Article - Vitamin E for people with non-alcoholic fatty liver disease.

Plain Language Summary

Non-alcoholic fatty liver disease (NAFLD) is a common liver condition affecting about 30% of people worldwide. Current treatments are not effective, and while lifestyle changes can help, they are often hard to maintain. Vitamin E has been suggested as a potential treatment because it may reduce oxidative stress, which is linked to the development of NAFLD. However, there is uncertainty about how effective vitamin E is for people with this condition. This systematic review and meta-analysis of 16 randomised controlled trials aimed to determine the benefits and risks of using vitamin E, either alone or with other vitamins and minerals, compared to a placebo or no treatment in individuals with NAFLD.

The results showed that vitamin E dosages ranged from 298 IU to 1000 IU, but durations were not given. Vitamin E reduced all cause mortality, serious adverse events, and improved quality of life, however poor quality data in these outcomes means that the authors were uncertain whether these observations were true effects. It was likely that vitamin E supplementation slightly improved markers of liver health. Vitamin E when used in combination with vitamin C improved markers of liver health, but again the evidence was uncertain.

It was concluded that given the low certainty of the evidence, it is unclear if vitamin E supplementation affects all-cause mortality, serious adverse events, quality of life, or non-serious adverse events in people with NAFLD. This study could be used by healthcare professionals to understand the potential effects of vitamin E on non-alcoholic fatty liver disease. However, on the basis of this evidence, it cannot be claimed to be effective for those with NAFLD.

Expert Review

Reviewer: Chloe Steele

14th Oct 2025

Conflict of interest

None

Take home message

Vitamin E supplementation is unlikely to affect NAFLD mortality and morbidity outcomes.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

Oxidative stress has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Vitamin E is an antioxidant vitamin, however there is uncertainty over its effects in those with NAFLD. This systematic review and meta-analysis aimed to determine the effects of vitamin E alone or in combination with other vitamins or minerals in those with NAFLD.

Method

This was a systematic review and meta-analysis of 16 randomised control trials containing 1066 adult and paediatric patients.
14 trials looked at vitamin E alone, 2 looked at vitamin E in combination with vitamin C.
13 trials were placebo controlled.
Daily dose of vitamin E ranged from 298 international units (IU) to 1000 IU.
Treatment durations ranged from 18-24 months.
The critical outcomes measured were all-cause mortality, liver-related mortality, and serious adverse events.

Results

Compared to placebo, the evidence was uncertain of vitamin E supplementation on all-cause mortality (risk ratio (RR) 3.45, 95% confidence interval (CI) 0.57 to 20.86; 3 trials, 351 participants; very low certainty evidence) and serious adverse events (RR 1.91, 95% CI 0.30 to 12.01; 2 trials, 283 participants; very low certainty evidence).
No data was found on liver-related mortality or morbidity.
Supplementation was shown to improve markers of liver function, with decreased serum alanine transaminase (ALT) (MD −9.29, 95% CI −13.69 to −4.89; 11 trials, 708 participants; moderate certainty evidence) and aspartate aminotransferase (AST) (MD −4.90, 95% CI −7.24 to −2.57; 11 trials, 695 participants; moderate certainty evidence) levels.
Compared to placebo, the evidence was uncertain surrounding the effects of vitamin E in combination with vitamin C on reducing liver function enzymes, serum ALT (MD −0.50, 95% CI −4.58 to 3.58; 2 trials, 133 participants; very low certainty evidence), AST (MD 0.09, 95% CI −3.39 to 3.57; 1 trial, 88 participants; very low certainty evidence), and gamma-glutamyl transferase (GGT) levels (MD 1.58, 95% CI −3.22 to 6.38; 1 trial, 88 participants; very low certainty evidence).

Conclusion

It is uncertain if vitamin E supplementation alone or in combination with vitamin C affects all-cause mortality, serious adverse events, or quality of life in individuals with NAFLD when compared to placebo or no intervention.

Clinical practice applications

Although NAFLD is associated with oxidative stress and vitamin E is an antioxidant, it is unlikely that vitamin E will improve mortality and morbidity outcomes in people with NAFLD.

Considerations for future research

Poor study design or a lack of studies looking at vitamin E use in relation to mortality and morbidity in those with NAFLD indicates that future studies should focus in these areas.

Expert reviews are written by nutrition professionals and academics with advanced qualifications to provide a critical appraisal of the article and implications for practice. Each review is peer-reviewed by a member of the NED Editorial Board. Find out more about our NED Expert Reviewers here.

Abstract

RATIONALE

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, affecting an estimated 3 in 10 people. The available treatment is far from optimal. Diet and lifestyle changes to promote weight loss and weight loss maintenance are the basic management of NAFLD, but these are difficult to achieve and maintain. Vitamin E has shown beneficial effects on oxidative stress, which plays a major role in the pathogenesis of NAFLD. However, there is uncertainty about the effects of vitamin E for people with NAFLD.

OBJECTIVES

To evaluate the beneficial and harmful effects of vitamin E alone, or vitamin E in combination with other vitamins or minerals, versus placebo or no intervention in people with NAFLD.

SEARCH METHODS

We used recommended Cochrane search methods. The latest search was performed on 2 February 2024.

ELIGIBILITY CRITERIA

We included randomised clinical trials that compared vitamin E alone, or in combination with other vitamins or minerals, at any dose, duration, and route of administration, versus placebo or no intervention, in people with NAFLD of any age, sex, or ethnic origin. We included participants with imaging techniques or histology-proven NAFLD and minimal alcohol intake, and participants with steatohepatitis who had liver biopsies.

OUTCOMES

Our critical outcomes were all-cause mortality, liver-related mortality, and serious adverse events. Our important outcomes were liver-related morbidity, health-related quality of life, non-serious adverse events, biochemical response, and imaging assessment of the degree of fatty liver.

RISK OF BIAS

We used Cochrane's RoB 2 tool to assess risk of bias for each of the predefined outcomes.

SYNTHESIS METHODS

We used standard Cochrane methods. We used GRADE to assess the certainty of evidence.

INCLUDED STUDIES

We included 16 randomised clinical trials involving 1066 paediatric and adult participants with NAFLD. Experimental groups received vitamin E alone (14 trials) or vitamin E in combination with vitamin C (2 trials). Control groups received placebo in 13 trials and no intervention in three trials. Daily dosages of oral vitamin E ranged from 298 international units (IU) to 1000 IU. Co-interventions were lifestyle and low-calorie diet interventions in 13 trials, ursodeoxycholic acid in one trial, unchanged diet and physical activity in one trial, and baseline treatments for type 2 diabetes in one trial. Nine trials had more than two intervention groups, but we used only the groups in which vitamin E alone or vitamin E in combination with vitamin C were compared with placebo or no intervention. In total, 7.9% (84/1066) of participants dropped out. Follow-up ranged from 2 months to 24 months.

SYNTHESIS OF RESULTS

Vitamin E versus placebo or no intervention The effects of vitamin E versus placebo or no intervention on all-cause mortality (risk ratio (RR) 3.45, 95% confidence interval (CI) 0.57 to 20.86; 3 trials, 351 participants; very low certainty evidence) and serious adverse events (RR 1.91, 95% CI 0.30 to 12.01; 2 trials, 283 participants; very low certainty evidence) are very uncertain. There were no data on liver-related mortality or liver-related morbidity. The effects of vitamin E versus placebo or no intervention on physical health-related quality of life (mean difference (MD) 0.74, 95% CI -0.52 to 2.01; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); psychosocial health-related quality of life (MD -0.57, 95% CI -4.11 to 2.97; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); and non-serious adverse events (RR 0.86, 95% CI 0.64 to 1.17; 2 trials, 283 participants; very low certainty evidence) are also very uncertain. There were no data on proportion of participants without a decrease in liver enzymes. Vitamin E likely slightly reduces serum alanine transaminase (ALT) (MD -9.29, 95% CI -13.69 to -4.89; 11 trials, 708 participants; moderate certainty evidence) and aspartate aminotransferase (AST) (MD -4.90, 95% CI -7.24 to -2.57; 11 trials, 695 participants; moderate certainty evidence) levels compared with placebo or no intervention. Vitamin E may slightly reduce serum alkaline phosphatase (ALP) levels (MD -5.21, 95% CI -9.88 to -0.54; 5 trials, 416 participants; very low certainty evidence), but the evidence is very uncertain. Vitamin E plus vitamin C versus placebo There were no data on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, and non-serious adverse events. The effects of vitamin E plus vitamin C on reducing serum ALT (MD -0.50, 95% CI -4.58 to 3.58; 2 trials, 133 participants; very low certainty evidence), AST (MD 0.09, 95% CI -3.39 to 3.57; 1 trial, 88 participants; very low certainty evidence), and gamma-glutamyl transferase (GGT) levels (MD 1.58, 95% CI -3.22 to 6.38; 1 trial, 88 participants; very low certainty evidence) are very uncertain. We identified three ongoing trials, and six trials are awaiting classification.

AUTHORS' CONCLUSIONS

Given the very low certainty evidence, we do not know if long-term treatment (18 months to 24 months) with vitamin E administered alone affects all-cause mortality, serious adverse events, quality of life, or non-serious adverse events in people with NAFLD when compared with placebo or no intervention. We found no data on liver-related mortality, liver-related morbidity, or proportion of participants without a decrease in liver enzymes. Vitamin E likely reduces ALT and AST slightly when compared with placebo, but whether this has any impact on the clinical course in people with NAFLD is unknown. The trials on vitamin E plus vitamin C did not report on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, or non-serious adverse events. Given the very low certainty evidence, we do not know the effects of vitamin E plus vitamin C on liver enzymes in people with NAFLD when compared with placebo.

FUNDING

Three trials disclosed no external funding. Five trials were industry funded. Five trials were funded by organisations with no vested interests. Three trials did not provide any information on clinical trial support or sponsorship.

REGISTRATION

Protocol: doi.org/10.1002/14651858.CD015033.