Key messages
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It is unclear whether long-term treatment (18 months to 24 months) with vitamin E alone or in combination with vitamin C affects death due to any cause, serious unwanted effects, health-related quality of life, or non-serious unwanted effects when compared with placebo (dummy pill) or no treatment.
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Vitamin E alone probably reduces alanine transaminase and aspartate aminotransferase (liver enzyme) levels slightly.
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Further research is needed to increase our confidence in the evidence.
What is non-alcoholic fatty liver disease?
Non-alcoholic fatty liver disease, recently renamed 'metabolic dysfunction-associated steatotic liver disease', is a common condition that affects people who may drink little to no alcohol. It is caused by too much fat in the liver (steatosis). People with non-alcoholic fatty liver disease can experience weakness, pain, or discomfort in the upper right side of the tummy. The disease affects not only the liver, but it is also associated with a high risk of high blood sugar, heart disease, and kidney disease.
What did we want to find out?
We wanted to find out if vitamin E alone, or in combination with other vitamins or minerals, was better than placebo (dummy pill) or no treatment in improving outcomes such as death due to any cause, serious unwanted effects, quality of life, liver-related death, liver-related illness, and non-serious unwanted effects. We also wanted to know if this treatment improves liver enzymes and steatosis, which indicate good liver function.
What did we do?
We searched for studies that looked at vitamin E alone or in combination with other vitamins or minerals compared to placebo or no treatment in adults and children with non-alcoholic fatty liver disease. We compared and summarised the results of the trials and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found 16 studies including 1066 adults and children with non-alcoholic fatty liver disease. The studies were performed in countries around the world and lasted between two months and two years.
Evidence for the effect of vitamin E administered alone on death from any cause, serious unwanted effects, quality of life, and non-serious unwanted events is very uncertain. Vitamin E alone likely slightly reduces serum alanine transaminase and aspartate aminotransferase levels (enzymes found in the liver) when compared with placebo or no intervention. Vitamin E may slightly reduce serum alkaline phosphatase (another liver enzyme) levels, but the evidence is very uncertain.
Evidence for the effect of vitamin E in combination with vitamin C on liver enzyme levels is very uncertain. No trial looking at vitamin E in combination with vitamin C reported on death due to any cause, serious unwanted effects, quality of life, or non-serious unwanted effects.
The outcomes liver-related death, liver-related illness, and numbers of people without a decrease in serum liver enzymes were not reported in any included study.
What are the limitations of the evidence?
Our confidence in the evidence ranged from very low to moderate. In general, we have little confidence in the evidence because few studies provided information on outcomes we were interested in; results varied across studies; and many of the studies were small. Further research is likely to change our results.
How up-to-date is this evidence?
The evidence is current to 2 February 2024.
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.
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.
We used recommended Cochrane search methods. The latest search was performed on 2 February 2024.
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.
Protocol: doi.org/10.1002/14651858.CD015033