Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials

Can Liu; Zeming Bai; Jingmin Cheng

doi:doi:10.11648/j.ajim.20251304.12

Research Article |

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Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials

Can Liu

, Zeming Bai

, Jingmin Cheng^*

Published in American Journal of Internal Medicine (Volume 13, Issue 4)

Received: 18 July 2025 Accepted: 29 August 2025 Published: 5 September 2025

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common fatty liver diseases, leading to biochemical and histological disorders in NAFLD. It is characterized by kinds of pathologies, ranging from simple non-alcoholic fatty liver (NAFL) to serious non-alcoholic steatohepatitis (NASH) with the complication of steatosis, fibrosis, NASH cirrhosis and hepatocellular carcinoma (HCC). The most important potential risk factors including insulin resistance and increased oxidative stress, especially vitamin E, have significant influence on the treatment for NAFLD. Vitamin E, as a key fat-soluble antioxidant, presents potential therapeutic value in the intervention of NAFLD. At present, there are differences in the intervention measures proposed by various studies, and the efficacy of corresponding intervention measures has not yet reached a unified conclusion. To analyze the relevant research on the combination therapy of vitamin E in NAFLD patients, and to explore the intervention effect of vitamin E combination therapy on their biochemical indicators and histological abnormalities. PubMed, EMBASE, Medline, Cochrane, ScienceDirect, Web of science, and Google Scholar Database were systematically searched to screen studies on the intervention effect of vitamin E combination therapy on NAFLD from January 2005 to April 2025. A total of 9 randomized controlled trials (RCT) were included, which included 885 participants with an average age of 35~48.04 years. The combination therapy of vitamin E had significantly improved liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT)) in NAFLD patients in most studies, and had also positive effects in improving liver histological parameters (NAFLD activity score (NAS), steatosis, fibrosis score, and inflammation), but there was heterogeneity among these studies. In addition, some studies did not observe significant improvement in ballooning, and only one study showed that combination therapy had no significant effect on liver function testing. The combination therapy of vitamin E has potential benefits in improving liver function indicators and some histological parameters in NAFLD patients, but its efficacy varies among studies. In the future, more high-quality and long-term RCT need to be conducted to further clarify the optimal regimen and applicable population of vitamin E in the treatment of NAFLD, providing a more comprehensive and reliable reference for clinical practice.

Published in	American Journal of Internal Medicine (Volume 13, Issue 4)
DOI	10.11648/j.ajim.20251304.12
Page(s)	54-63
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Vitamin E, Non-alcoholic Fatty Liver Disease, RCTs, Systematic Review

1. Introduction

Non-alcoholic fatty liver disease (NAFLD), one of the common chronic liver disease, is characterized by hepatic fat accumulation exceeding 5% of liver weight

[1]

, encompassing a disease spectrum from simple non-alcoholic fatty liver (NAFL) to serious non-alcoholic steatohepatitis (NASH), which may further progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC)

[2]

. Epidemiologically, NAFLD affects over 30% of the global adult population, with a higher prevalence in industrialized nations reaching 40-50% due to sedentary lifestyles and high-calorie diets

[3-5]

. The pathogenesis of NAFLD is multifactorial, with insulin resistance (IR) as a central driver

[6]

. IR promotes hepatic de novo lipogenesis and impairs triglyceride export, leading to lipid accumulation

[7]

. Importantly, accumulated lipids in hepatocytes induce mitochondrial dysfunction, which enhances the production of reactive oxygen species (ROS)

[8]

. Excessive ROS overwhelms the cellular antioxidant defense system, triggering oxidative stress—a key contributor to hepatocellular injury, inflammation, and fibrosis

[9]

. Oxidative stress mediates lipid peroxidation, generating toxic byproducts (e.g., malondialdehyde) that activate hepatic stellate cells, initiating fibrogenesis

[10]

. NAFLD also exhibits strong comorbidities with metabolic syndrome components: 50-70% of NAFLD patients have type 2 diabetes mellitus (T2DM), 60-80% are obese, and hyperlipidemia is present in 70-80% of cases, creating a bidirectional relationship where metabolic derangements exacerbate liver injury and vice versa

[11]

Despite its high prevalence and related metabolic syndrome, there is no standard drug approved for the treatment of NAFLD

[12]

. Currently, lowering the calorie intake, weight loss, and exercise is recommended for the treatment of NAFLD. In addition, some drugs including Silymarin, symbiotic, alpha-tocopherol and spironolactone have also been tried. However, recommending these agents may be a difficult thing due to their side effects and safety in NAFLD

[13, 14]

. Consequently, it seems necessary to find relatively safe drugs for the treatment of NAFLD. Beta vulgaris, Silymarin and Spironolactone reduce blood sugar, induce glucose storage as glycogen and has been used to treat different liver disorders, and the level of liver enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) is also decreased

[11, 15, 16]

. Conjugated linoleic acid (CLA), one of the promising dietary supplements, has anti-diabetic, anti-obesity and anti-inflammatory effects, acting through a variety of mechanisms to prevent and improve NAFLD

[17]

. However, vitamin E, a potent antioxidant, significant improves biochemical and histological abnormalities related with NAFLD, on account of the absence of adverse effects

[18]

. And this adjuvant medicine, has also potential benefits for the treatment of NAFLD

[19]

. Among potential agents, vitamin E (α-tocopherol, the most biologically active isoform) has garnered attention for its robust antioxidant properties and favorable safety profile

[20]

. As a lipid-soluble antioxidant, vitamin E exerts its effects through multiple mechanisms: (1) It scavenges lipid peroxyl radicals by donating a hydrogen atom from its chromanol ring, terminating lipid peroxidation chains and protecting membrane phospholipids from oxidative damage—critical for preserving hepatocyte integrity

[21]

. (2) It preserves mitochondrial function by reducing ROS-induced damage to mitochondrial DNA and respiratory chain complexes, thereby decreasing further ROS production

[22]

. (3) It upregulates the Nrf2-Keap1 pathway, a master regulator of antioxidant genes (e.g., HO-1, SOD), enhancing endogenous antioxidant capacity

[23]

Beyond NAFLD, vitamin E’s antioxidant actions contribute to its protective role in various oxidative stress-related diseases

[24]

. In cardiovascular disease, it inhibits low-density lipoprotein (LDL) oxidation, a key step in atherogenesis, reducing the risk of myocardial infarction in high-risk populations

[25]

. In T2DM, it ameliorates oxidative stress-induced insulin resistance by preserving pancreatic β-cell function and improving insulin signaling in peripheral tissues

[26]

. In neurodegenerative diseases (e.g., Alzheimer’s), it mitigates oxidative damage to neurons, slowing cognitive decline

[27]

. These pleiotropic effects are clinically relevant for NAFLD patients, who often face comorbid cardiovascular and metabolic risks, making vitamin E a potential multitarget intervention

[28]

. Although there have been some studies where authors have compared the efficacy of vitamin E vs. placebo or vitamin E combination therapy vs. monotherapy among all population groups

[11]	Afzali N, Ebadi SS, Afzali H, Sharif MR, Vazirian M, Ebadi SA, et al. Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial [J]. Hepatitis Monthly. 2020, 20(7): e102125. https://doi.org/10.5812/hepatmon.102125 View Article
[16]	Polyzos SA, Kountouras J, Mantzoros CS, Polymerou V, Katsinelos P. Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial [J]. Diabetes Obesity & Metabolism. 2017, 19(12): 1805-9. https://doi.org/10.1111/dom.12989 View Article
[17]	Abedi R, Aref-Hosseini SR, Khoshbaten M, Ebrahimi-Mameghani M, Laleh HJ, Jalalypour F, et al. The Effect of conjugated linoleic acid (CLA) on inflammatory factors in Non-Alcoholic Fatty Liver Disease (NAFLD): A randomized controlled clinical trial [J]. Progress in Nutrition. 2018, 20: 173-81. https://doi.org/10.23751/pn.v20i2-S.5593 View Article
[19]	Ekhlasi G, Zarrati M, Agah S, Hosseini AF, Hosseini S, Shidfar S, et al. Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease [J]. EXCLI journal. 2017, 16: 278-90. https://doi.org/10.17179/excli2016-846 View Article
[29]	Akhondi-Meybodi M, Baghbanian M. The effect of silymarin and vitamin E in the treatment of non-alcoholic fatty liver disease: A randomized, double-blind clinical trial [J]. United European Gastroenterology Journal. 2019, 7(8): 758. https://doi.org/10.1177/205064061985467 View Article
[30]	Kedarisetty CK, Bhardwaj A, Kumar G, et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study [J]. Indian J Gastroenterol. 2021; 40(1): 41-49. https://doi.org/10.1007/s12664-020-01131-x View Article
[31]	Mir BA, Sharma B, Sharma R, et al. A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL [J]. J Clin Exp Hepatol. 2024; 14(5): 101398. https://doi.org/10.1016/j.jceh.2024.101398 View Article
[32]	Khaliq A, Badshah H, Shah Y. Combination therapy with vitamin E and ertugliflozin in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a randomized clinical trial [J]. Ir J Med Sci. 2025; 194(3): 899-908. https://doi.org/10.1007/s11845-025-03945-0 View Article
[33]	Song Y, Ni W, Zheng M, et al. Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study [J]. Cell Rep Med. 2025; 6(2): 101939. https://doi.org/10.1016/j.xcrm.2025.101939 View Article

[11, 16, 17, 19, 29-33]

, systematic reviews that concurrently observed the effects of the combined multiple drugs plus vitamin E vs. vitamin E on NAFLD outcomes for the adult population are scarce. Given its established antioxidant mechanisms, favorable safety, and potential to address both liver-specific and systemic oxidative stress, this systematic review aims to synthesize evidence on vitamin E’s therapeutic efficacy in adult NAFLD.

2. Methods

2.1. Information Sources

Two independent reviewers conducted an exhaustive literature search via electronic databases, adhering strictly to the PRISMA guidelines for systematic reviews. PubMed, EMBASE, Medline, Cochrane, ScienceDirect, Web of science, Google Scholar and clinical trial directories were searched for peer-reviewed randomized control trials conducted between January 2005 and April 2025. Two search themes were employed to query the databases, with the two themes combined via the Boolean operator ‘AND’. The following keywords were used: ‘Vitamin E’, ‘Tocopherols’, ‘Tocotrienols’, ‘Non-alcoholic Fatty Liver Disease’, ‘NAFLD’, ‘Fatty Liver, Non-alcoholic’, ‘Liver, Non-alcoholic Fatty’, ‘Non-alcoholic Steatohepatitis’, ‘NASH’.

2.2. Inclusion and Exclusion Criteria

The inclusion criteria were as follows: (a) RCTs researches; (b) studies recruiting adult population (age ≥18); (c) biochemical markers (ALT, AST) and/or histological markers (steatosis, ballooning, inflammation, and fibrosis); (d) NAFLD/NASH must be diagnosed by radiology or histology; (e) published in English.

The exclusion criteria were as follows: (a) all studies conducted on children and adolescent population, (b) other common chronic liver diseases and secondary steatosis (severe alcohol consumption, hepatitis B, autoimmune hepatitis, etc.); (c) studies that were not RCTs were excluded from the study.

2.3. Data Extraction and Study Selection

Two researchers evaluated the studies, and in cases of disagreement, a third researcher was consulted. Relevant information was extracted from and organized in the included studies using Microsoft Excel, encompassing basic details (such as gender and age), intervention methods, serum liver function indicators (ALT, AST, ALP, GGT), and pathological parameters (NAS, ballooning degeneration, fibrosis).

A total of 7,665 studies were identified through the literature search. Of these, 2,142 were excluded due to duplication, and 5,336 were excluded as irrelevant records. The researchers then manually screened 192 studies, with a further 178 excluded after reviewing their titles and abstracts. Ultimately, 9 randomized controlled trials (RCTs) were included in the final analysis.

Download: Download full-size image

Figure 1. Describes the literature review process.

3. Results

A total of 9 RCTs published between January 2005 and April 2025 were identified. All the trials included a total of 867 participants with the mean age ranging between 30 and 65 years. The duration of studies ranged from 2 months to 24 months. Table 1 includes the RCTs added in chronological order and summarizes the population demographics and interventions used.

Table 1. Summary of patient demographics, study design, and study interventions in the included RCTs.

Authors and year

Type of study

Duration of study

Sample size

Mean age

Gender

Interventions used

Akhondi-Meybodi et al. 2020

[

29 ]

RCT

4 months

Group1 (Vitamin E): 40

Group2 (Silymarin): 40

Group1: 44.2

Group2: 43.7

Group1: Females: 38%

Males: 62%

Group2: Females: 33%

Males: 67%

Group1: Vitamin E 400 IU once Daily

Group2: silymarin 140 mg BID once daily

Ekhlasi et al. 2017

9 ]

double-blinded RCT

2 months

Group1 (symbiotic): 15

Group2 (alpha-tocopherol): 15

Group3 (symbiotic+alpha-tocopherol): 15

Group4 (placebo): 15

Females: 20%

Males: 80%

Group1: symbiotic 1 g once daily

Group2: alpha-tocopherol 400 IU once daily

Group3: symbiotic 1 g, alpha-tocopherol 400 IU once daily

Group4: placebo 400 IU once daily

Polyzos et al. 2017

6 ]

RCT

13 months

Group1 (spironolactone+ vitamin E): 14

Group2 (Vitamin E): 17

Group1: Females: 85.7%

Males: 14.3%

Group2: Females: 64.7%

Males: 35.3%

Group1: spironolactone 25 mg once daily,

vitamin E 400 IU/day

Group2: Vitamin E 400 IU/day

Abedi et al. 2018

7 ]

single-blind RCT

2 months

Group1 (Vitamin E+soft gel CLA): 19

Group2 (vitamin E): 19

Group1: 36.7

Group2: 38.6

Group1: Females: 89.5%

Males: 10.5%

Group2: Females: 84.2%

Males: 15.8%

Group1: Vitamin E 400, soft gel CLA 3000 mg/day

Group2: vitamin E 400 mg/day

Afzali et al. 2020

[

11 ]

double-blind RCT

6 months

Group1 (Beta vulgaris): 60

Group2 (Placebo): 57

Group1: 47.5

Group2: 46.4

Group1: Females: 45%

Males: 55%

Group2: Females: 49.1%

Males: 50.9%

Group1: vitamin E pearl (300 IU/twice

daily), Livergol tablet (140 mg/daily),

Beta vulgaris capsule (400 mg/daily)

Group2: vitamin E pearl (300 IU/twice daily), Livergol tablet (140 mg/daily), instead of Beta vulgaris capsule (400 mg/daily)

Chandan et al 2021

[

30 ]

RCT

12 months

Group1 (Pentoxyphylline+Vitamin E): 36

Group2 (Vitamin E): 33

Group1: 40

Group2: 35

Group1: Males/Females 33/3

Group2: Males/Females 28/5

Group1: Pentoxyphylline (400 mg/ thrice daily), vitamin E (400 IU/ twice daily)

Group2: vitamin E (400 IU/ twice daily)

Bilal et al 2024

[

31 ]

RCT

6 months

Group1 (Saroglitazar): 44

Group2 (Vitamin E): 41

Group3 (Saroglitazar +Vitamin E): 47

Group4 (control arm): 43

Group1: Females: 19

Males: 25

Group2: Females: 17

Males: 24

Group3: Females: 14

Males: 33

Group4: Females: 13

Males: 30

Group1: Saroglitazar (4 mg/ daily alone)

Group2: vitamin E (800 IU/ daily alone)

Group3: Saroglitazar (4 mg/ daily alone), vitamin E (800 IU/ daily alone)

Group4: control arm

Khaliq

[

32 ]

double-blind RCT

6 months

Group1 (vitamin E): 42

Group2 (pioglitazone): 43

Group3 (ertugliflozin): 44

Group4 (vitamin E + ertugliflozin): 44

30-65

Group1: Females: 11

Males: 31

Group2: Females: 10

Males: 33

Group3: Females: 9

Males: 35

Group4: Females: 10

Males: 34

Group1: vitamin E (800 IU/ once daily)

Group2: pioglitazone (30 mg/ once daily)

Group3: ertugliflozin (15 mg/ once daily)

Group4: ertugliflozin (15 mg/ once daily)

vitamin E (800 IU/ once daily)

[

33 ]

double-blind RCT

24 months

Group1 (Vitamin E): 58

Group2 (placebo): 66

Group1: 37.9

Group2: 39.0

Group1: Females: 16

Males: 42

Group2: Females: 16

Males: 50

Group1: vitamin E (300 mg / daily)

Group2: placebo (300 mg / daily)

The study by Akhondi-Meybodi et al. did not clearly define the randomization strategy and combine vitamin E with silymarin for the therapy of NAFLD

[29]

. One double-blinded RCT compared a combination therapy of symbiotic, alpha-tocopherol, symbiotic and alpha-tocopherol, and placebo

[19]

; the other double-blinded study compared Beta vulgaris therapy and placebo

[11]

. One RCT compared vitamin E monotherapy and vitamin E combination therapy with low-dose spironolactone

[16]

. One single-blinded RCT compared a combination therapy of vitamin E and soft gel CLA

[17]

. One RCT compared vitamin E monotherapy and vitamin E combination therapy with Pentoxyphylline

[30]

. Another RCT compared control and saroglitazar, vitamin E, as well as combination therapy

[31]

. One double-blinded RCT compared vitamin E and pioglitazone, ertugliflozin, as well as a combination therapy of vitamin E and ertugliflozin

[32]

. Another double-blinded RCT compared vitamin E and placebo

[33]

. All the RCTs used varying doses of vitamin E, ranging from 300 IU to 800 IU

[11]	Afzali N, Ebadi SS, Afzali H, Sharif MR, Vazirian M, Ebadi SA, et al. Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial [J]. Hepatitis Monthly. 2020, 20(7): e102125. https://doi.org/10.5812/hepatmon.102125 View Article
[16]	Polyzos SA, Kountouras J, Mantzoros CS, Polymerou V, Katsinelos P. Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial [J]. Diabetes Obesity & Metabolism. 2017, 19(12): 1805-9. https://doi.org/10.1111/dom.12989 View Article
[17]	Abedi R, Aref-Hosseini SR, Khoshbaten M, Ebrahimi-Mameghani M, Laleh HJ, Jalalypour F, et al. The Effect of conjugated linoleic acid (CLA) on inflammatory factors in Non-Alcoholic Fatty Liver Disease (NAFLD): A randomized controlled clinical trial [J]. Progress in Nutrition. 2018, 20: 173-81. https://doi.org/10.23751/pn.v20i2-S.5593 View Article
[29]	Akhondi-Meybodi M, Baghbanian M. The effect of silymarin and vitamin E in the treatment of non-alcoholic fatty liver disease: A randomized, double-blind clinical trial [J]. United European Gastroenterology Journal. 2019, 7(8): 758. https://doi.org/10.1177/205064061985467 View Article
[30]	Kedarisetty CK, Bhardwaj A, Kumar G, et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study [J]. Indian J Gastroenterol. 2021; 40(1): 41-49. https://doi.org/10.1007/s12664-020-01131-x View Article
[31]	Mir BA, Sharma B, Sharma R, et al. A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL [J]. J Clin Exp Hepatol. 2024; 14(5): 101398. https://doi.org/10.1016/j.jceh.2024.101398 View Article
[32]	Khaliq A, Badshah H, Shah Y. Combination therapy with vitamin E and ertugliflozin in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a randomized clinical trial [J]. Ir J Med Sci. 2025; 194(3): 899-908. https://doi.org/10.1007/s11845-025-03945-0 View Article
[33]	Song Y, Ni W, Zheng M, et al. Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study [J]. Cell Rep Med. 2025; 6(2): 101939. https://doi.org/10.1016/j.xcrm.2025.101939 View Article

[11, 16, 17, 29-33]

. Silymarin, symbiotic, alpha-tocopherol, symbiotic and alpha-tocopherol, spironolactone, soft gel CLA, Beta vulgaris, pentoxyphylline, saroglitazar, pioglitazone and ertugliflozin were the common co-intervention used in the nine RCTs

[11]	Afzali N, Ebadi SS, Afzali H, Sharif MR, Vazirian M, Ebadi SA, et al. Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial [J]. Hepatitis Monthly. 2020, 20(7): e102125. https://doi.org/10.5812/hepatmon.102125 View Article
[16]	Polyzos SA, Kountouras J, Mantzoros CS, Polymerou V, Katsinelos P. Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial [J]. Diabetes Obesity & Metabolism. 2017, 19(12): 1805-9. https://doi.org/10.1111/dom.12989 View Article
[17]	Abedi R, Aref-Hosseini SR, Khoshbaten M, Ebrahimi-Mameghani M, Laleh HJ, Jalalypour F, et al. The Effect of conjugated linoleic acid (CLA) on inflammatory factors in Non-Alcoholic Fatty Liver Disease (NAFLD): A randomized controlled clinical trial [J]. Progress in Nutrition. 2018, 20: 173-81. https://doi.org/10.23751/pn.v20i2-S.5593 View Article
[19]	Ekhlasi G, Zarrati M, Agah S, Hosseini AF, Hosseini S, Shidfar S, et al. Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease [J]. EXCLI journal. 2017, 16: 278-90. https://doi.org/10.17179/excli2016-846 View Article
[29]	Akhondi-Meybodi M, Baghbanian M. The effect of silymarin and vitamin E in the treatment of non-alcoholic fatty liver disease: A randomized, double-blind clinical trial [J]. United European Gastroenterology Journal. 2019, 7(8): 758. https://doi.org/10.1177/205064061985467 View Article
[30]	Kedarisetty CK, Bhardwaj A, Kumar G, et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study [J]. Indian J Gastroenterol. 2021; 40(1): 41-49. https://doi.org/10.1007/s12664-020-01131-x View Article
[31]	Mir BA, Sharma B, Sharma R, et al. A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL [J]. J Clin Exp Hepatol. 2024; 14(5): 101398. https://doi.org/10.1016/j.jceh.2024.101398 View Article
[32]	Khaliq A, Badshah H, Shah Y. Combination therapy with vitamin E and ertugliflozin in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a randomized clinical trial [J]. Ir J Med Sci. 2025; 194(3): 899-908. https://doi.org/10.1007/s11845-025-03945-0 View Article
[33]	Song Y, Ni W, Zheng M, et al. Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study [J]. Cell Rep Med. 2025; 6(2): 101939. https://doi.org/10.1016/j.xcrm.2025.101939 View Article

[11, 16, 17, 19, 29-33]

Eight of the nine RCTs noted significant improvements in liver function tests

[11]	Afzali N, Ebadi SS, Afzali H, Sharif MR, Vazirian M, Ebadi SA, et al. Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial [J]. Hepatitis Monthly. 2020, 20(7): e102125. https://doi.org/10.5812/hepatmon.102125 View Article
[17]	Abedi R, Aref-Hosseini SR, Khoshbaten M, Ebrahimi-Mameghani M, Laleh HJ, Jalalypour F, et al. The Effect of conjugated linoleic acid (CLA) on inflammatory factors in Non-Alcoholic Fatty Liver Disease (NAFLD): A randomized controlled clinical trial [J]. Progress in Nutrition. 2018, 20: 173-81. https://doi.org/10.23751/pn.v20i2-S.5593 View Article
[19]	Ekhlasi G, Zarrati M, Agah S, Hosseini AF, Hosseini S, Shidfar S, et al. Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease [J]. EXCLI journal. 2017, 16: 278-90. https://doi.org/10.17179/excli2016-846 View Article
[29]	Akhondi-Meybodi M, Baghbanian M. The effect of silymarin and vitamin E in the treatment of non-alcoholic fatty liver disease: A randomized, double-blind clinical trial [J]. United European Gastroenterology Journal. 2019, 7(8): 758. https://doi.org/10.1177/205064061985467 View Article
[30]	Kedarisetty CK, Bhardwaj A, Kumar G, et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study [J]. Indian J Gastroenterol. 2021; 40(1): 41-49. https://doi.org/10.1007/s12664-020-01131-x View Article
[31]	Mir BA, Sharma B, Sharma R, et al. A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL [J]. J Clin Exp Hepatol. 2024; 14(5): 101398. https://doi.org/10.1016/j.jceh.2024.101398 View Article
[32]	Khaliq A, Badshah H, Shah Y. Combination therapy with vitamin E and ertugliflozin in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a randomized clinical trial [J]. Ir J Med Sci. 2025; 194(3): 899-908. https://doi.org/10.1007/s11845-025-03945-0 View Article
[33]	Song Y, Ni W, Zheng M, et al. Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study [J]. Cell Rep Med. 2025; 6(2): 101939. https://doi.org/10.1016/j.xcrm.2025.101939 View Article

[11, 17, 19, 29-33]

. Six studies noted a significant improvement in both ALT and AST

[11]	Afzali N, Ebadi SS, Afzali H, Sharif MR, Vazirian M, Ebadi SA, et al. Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial [J]. Hepatitis Monthly. 2020, 20(7): e102125. https://doi.org/10.5812/hepatmon.102125 View Article
[19]	Ekhlasi G, Zarrati M, Agah S, Hosseini AF, Hosseini S, Shidfar S, et al. Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease [J]. EXCLI journal. 2017, 16: 278-90. https://doi.org/10.17179/excli2016-846 View Article
[29]	Akhondi-Meybodi M, Baghbanian M. The effect of silymarin and vitamin E in the treatment of non-alcoholic fatty liver disease: A randomized, double-blind clinical trial [J]. United European Gastroenterology Journal. 2019, 7(8): 758. https://doi.org/10.1177/205064061985467 View Article
[30]	Kedarisetty CK, Bhardwaj A, Kumar G, et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study [J]. Indian J Gastroenterol. 2021; 40(1): 41-49. https://doi.org/10.1007/s12664-020-01131-x View Article
[31]	Mir BA, Sharma B, Sharma R, et al. A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL [J]. J Clin Exp Hepatol. 2024; 14(5): 101398. https://doi.org/10.1016/j.jceh.2024.101398 View Article
[32]	Khaliq A, Badshah H, Shah Y. Combination therapy with vitamin E and ertugliflozin in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a randomized clinical trial [J]. Ir J Med Sci. 2025; 194(3): 899-908. https://doi.org/10.1007/s11845-025-03945-0 View Article
[33]	Song Y, Ni W, Zheng M, et al. Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study [J]. Cell Rep Med. 2025; 6(2): 101939. https://doi.org/10.1016/j.xcrm.2025.101939 View Article

[11, 19, 29-33]

; two noted improvement in ALP

[19, 32]

, and one noted improvement in GGT only

[32]

. Abedi et al. reported additional improvements in ALT/AST ratio

[17]

. Polyzos et al. did not report any improvements in liver function tests with a combination therapy of vitamin E and spironolactone

[16]

(Table 2).

When liver histological parameters were evaluated, the treatment groups showed only limited improvements. Polyzos et al., Bilal et al., Khaliq et al. and Yu et al. reported improvement in steatosis

[16, 31-33]

, and Abedi et al., Chandan et all. and Yu et al. reported an improvement in inflammation

[17, 30, 33]

. Chandan et all. and Yu et al. showed improvement in NAFLD Activity Score NAS

[30, 33]

, Polyzos et al., Bilal et al. and Khaliq et al. reported improvement in fibrosis score

[19]

. Polyzos et al. and Yu et al showed no improvement in ballooning

[16, 33]

However, it must be noted that several markers of hepatic histological response (such as NAS, steatosis, fibrosis, ballooning, and inflammation) were not recorded in several studies

[11]	Afzali N, Ebadi SS, Afzali H, Sharif MR, Vazirian M, Ebadi SA, et al. Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial [J]. Hepatitis Monthly. 2020, 20(7): e102125. https://doi.org/10.5812/hepatmon.102125 View Article
[16]	Polyzos SA, Kountouras J, Mantzoros CS, Polymerou V, Katsinelos P. Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial [J]. Diabetes Obesity & Metabolism. 2017, 19(12): 1805-9. https://doi.org/10.1111/dom.12989 View Article
[17]	Abedi R, Aref-Hosseini SR, Khoshbaten M, Ebrahimi-Mameghani M, Laleh HJ, Jalalypour F, et al. The Effect of conjugated linoleic acid (CLA) on inflammatory factors in Non-Alcoholic Fatty Liver Disease (NAFLD): A randomized controlled clinical trial [J]. Progress in Nutrition. 2018, 20: 173-81. https://doi.org/10.23751/pn.v20i2-S.5593 View Article
[19]	Ekhlasi G, Zarrati M, Agah S, Hosseini AF, Hosseini S, Shidfar S, et al. Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease [J]. EXCLI journal. 2017, 16: 278-90. https://doi.org/10.17179/excli2016-846 View Article
[29]	Akhondi-Meybodi M, Baghbanian M. The effect of silymarin and vitamin E in the treatment of non-alcoholic fatty liver disease: A randomized, double-blind clinical trial [J]. United European Gastroenterology Journal. 2019, 7(8): 758. https://doi.org/10.1177/205064061985467 View Article
[30]	Kedarisetty CK, Bhardwaj A, Kumar G, et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study [J]. Indian J Gastroenterol. 2021; 40(1): 41-49. https://doi.org/10.1007/s12664-020-01131-x View Article
[31]	Mir BA, Sharma B, Sharma R, et al. A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL [J]. J Clin Exp Hepatol. 2024; 14(5): 101398. https://doi.org/10.1016/j.jceh.2024.101398 View Article
[32]	Khaliq A, Badshah H, Shah Y. Combination therapy with vitamin E and ertugliflozin in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a randomized clinical trial [J]. Ir J Med Sci. 2025; 194(3): 899-908. https://doi.org/10.1007/s11845-025-03945-0 View Article

[11, 16, 17, 19, 29-32]

Table 2. Summarizes the effects of vitamin E on biochemical and histological markers of NAFLD.

Author and year

Improvement in liver function tests (ALT, AST, ALP, GGT)

Improvement in NAFLD Activity Score (NAS)

Improvement in steatosis

Improvement in fibrosis score

Improvement in ballooning

Improvement in inflammation

Akhondi-Meybodi et al. 2020

[

29 ]

significant decrease in ALT and AST in the treatment group

Not recorded

Ekhlasi et al. 2017

9 ]

significant decrease in AST, ALT and ALP level

Not recorded

Polyzos et al. 2017

6 ]

Not recorded

Yes

Not recorded

Abedi et al. 2018

7 ]

significant decrease in ALT/AST ratio in the treatment group

Not recorded

Yes

Afzali et al. 2020

[

11 ]

significant decrease in AST and ALT in the treatment group

Not recorded

Chandan et al 2021

[

30 ]

significant decrease in ALT level

Yes

Not recorded

Yes

Not recorded

Yes

Bilal et al 2024

[

31 ]

significant decrease in AST and ALT level

Yes

Not recorded

Khaliq et al 2025

[

32 ]

significant decrease in AST, ALT, ALP and GGT level

Not recorded

Yes

Not recorded

Yu et al 2025

[

33 ]

significant decrease in AST and ALT

Yes

No. of results showing improvement

No. of results showing no improvement

No. of results not recorded

GGT: Gamma-Glutamyl Transpeptidase

4. Discussion

NAFLD is closely associated with metabolic syndrome

[34]

. The relation of NAFLD with insulin resistance, obesity, type II diabetes mellitus and hyperlipidemia is well confirmed. The progression of the disease is attributed to ROS, mitochondrial dysfunction, endotoxin-induced cytokine release, oxidative stress and metabolic changes

[35]

. According to the progression of NAFLD, pharmacological therapies should be considered to avoid more serious consequences. However, some medicines such as Silymarin, symbiotic, alpha-tocopherol and spironolactone are not widely recommended due to its own side effects and unapproved validity in NAFLD. Interestingly, vitamin E, an anti-oxidant, reduces reactive oxygen species, improves the antioxidants and decreases the hepatic steatosis, fibrosis, ballooning and inflammation, and has been investigated to treat NAFLD

[18]

. Therefore, vitamin E is broadly recommended for the therapy of NAFLD by the different scientific societies from Europe, America, and Asia-Pacific regions

[36]

Research by Afzali et al. reported that Beta vulgaris has positive effects on the biochemical parameters of patients with NAFLD, and lowers ALT and AST levels. Moreover, Beta vulgaris alongside NAFLD therapy such as vitamin E and Silybum marianum has satisfactory clinical results due to its high availability and low cost

[11]

. Akhondi et al. noted that combination therapy with vitamin E and silymarin can improve the conditions of patients with NAFLD. Silymarin acted as a natural ingredient of milk thistle and an antioxidant which may reduce liver damage by decreasing ALT and AST levels

[29]

. In the Polyzos et al. study, despite biochemical markers (ALT and AST levels) in NAFLD did not change, insulin resistance and steatosis were significantly decreased in the combination group of low-dose spironolactone plus vitamin E

[16]

. Study by Abedi et al. showed that CLA, a mixture of unsaturated isomers of octadecadienoic acid, has an anti-inflammatory effects and supplementation of CLA lead to the decrease of inflammatory level and (ALT/AST) ratio

[17]

. In addition to CLA, vitamin E has also a strong anti-oxidative property and could positively impact ALT, AST and inflammation in patients with NAFLD

[37]

. A crucial finding in another study suggested that ALT, AST and ALP levels were significantly lower in patients with NAFLD in the symbiotic alongside alpha-tocopherol intervention groups

[19]

. Study by Chandan et al.

[30]

indicated a significant decrease in ALT levels, which further supported the potential of the intervention (e.g., vitamin E supplementation) in improving hepatocellular injury, as ALT, a sensitive marker of liver damage, reflected the alleviation of hepatic inflammation and structural impairment. The significant decreases in AST and ALT levels were observed in the study of Bilal et al

[31]

and Yu et al

[33]

, collectively supporting that the intervention (e.g., vitamin E supplementation) may exert a protective effect on hepatocellular integrity, as these enzymes were reliable indicators of liver cell damage, and their reduction reflects mitigated hepatic injury and improved liver function. The significant reduction in AST, ALT, ALP, and GGT levels reported by Khaliq et al

[32]

underscored a comprehensive improvement in liver function, as these enzymes collectively reflected hepatocellular integrity (AST, ALT), bile duct function (ALP), and hepatobiliary detoxification capacity (GGT), thereby indicating that the intervention in question may exert multi-faceted protective effects on hepatic structure and physiological processes.

The studies above indicated that the potential of vitamin E in the NAFLD therapy significantly improves liver function (ALT and AST levels) and histological abnormalities such as steatosis and inflammation in NAFLD. The consequences of our study are in agreement with those of Loguercio et al.

[38]

and Pietu et al.

[39]

, in which the combined other drugs plus vitamin E reduced biochemical markers in patients with NAFLD, especially ALT and AST levels. However, the impact of vitamin E on biochemical and hepatic histological parameters in NAFLD patients have been represented discrepantly in the relevant research. The present study demonstrated that vitamin E is able to improve liver steatosis and inflammation, yet hepatic fibrosis and ballooning are not significant change. One research by Derakhshandeh-Rishehri et al.

[1]

reported Realsil intake decreased circulating GGT level and was not associated with the improvement of AST and ALT levels. In that study, mean scores for liver histological markers such as steatosis, inflammation, and ballooning were reduced with the combined vitamin E and pioglitazone

[40]

. However, a meta-analysis showed all hepatic histological indicators, including liver steatosis, fibrosis, ballooning and inflammation, were significantly improved in patients with NASH

[41]

. In addition, Fukui et al.

[42]

reported a significant improvement in liver function such as ALT, AST and GGT with the use of vitamin E. Even so, the evidence indicated that high-dose vitamin E could increase the risk of mortality

[43]

, though the relation was not well confirmed

[44, 45]

. Also, the present study included only three blinded and two open-label trials in the analysis with different baseline morbidities and three of the five were followed for less than six months

[46]

. Thus, further investigations are necessary for the safety profile of vitamin E in the clinical practice, especially on long-term follow up.

Limitations

Our systematic review has some limitations; duration of intervention was relatively short in the RCTs. The sample sizes in the current RCTs were relatively small. Moreover, the RCTs did not investigate one or more crucial factors useful for monitoring disease progression in NAFLD. The longer duration of intervention and larger samples are necessary to verify the safety of daily vitamin E alone or combined with other anti-oxidants in future research.

5. Conclusions

Vitamin E is a potential antioxidant useful for the treatment of NAFLD. Our systematic review suggests that vitamin E therapy provides several biochemical and histological improvements in NAFLD. However, the association of vitamin E therapy with liver disease pathology such as NAFLD Activity Score, fibrosis and ballooning are not significantly observed. Additionally, the conclusion on the safety and efficacy of proposed treatments is limited due to the short duration of trials. Thus, vitamin E should be more widely used as a potent antioxidant or an adjuvant due to its potential benefit for the therapy of NAFLD in clinical practice. Future research could explore the underlying mechanisms by which vitamin E exerts its biochemical and histological benefits in NAFLD, as well as investigate whether modifying factors such as dosage regimens, patient genetic backgrounds, or concurrent metabolic conditions might enhance its effects on key pathological features like NAFLD Activity Score, fibrosis, and ballooning, while also extending trial durations to better assess long-term safety and efficacy.

Abbreviations

NAFLD	Non-alcoholic Fatty Liver Disease
NAFL	Non-Alcoholic Fatty Liver
NASH	Non-alcoholic Steatohepatitis
HCC	Hepatocellular Carcinoma
RCT	Randomized Controlled Trials
AST	Aspartate Aminotransferase
ALT	Alanine Aminotransferase
ALP	Alkaline Phosphatase
GGT	Gamma Glutamyl Transferase
NAS	NAFLD Activity Score
IR	Insulin Resistance
ROS	Reactive Oxygen Species
T2DM	Type 2 Diabetes Mellitus
CLA	Conjugated Linoleic Acid
LDL	Low-density Lipoprotein

Acknowledgments

The authors thank all of the people who participated in this study.

Author Contribution

Can Liu: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Writing – original draft

Zeming Bai: Data curation, Software

Jingmin Cheng: Conceptualization, Supervision, Writing – review & editing

Conflicts of Interest

The authors declare that there is no conflict of interest.

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Liu, C., Bai, Z., Cheng, J. (2025). Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials. American Journal of Internal Medicine, 13(4), 54-63. https://doi.org/10.11648/j.ajim.20251304.12

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Liu, C.; Bai, Z.; Cheng, J. Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials. Am. J. Intern. Med. 2025, 13(4), 54-63. doi: 10.11648/j.ajim.20251304.12

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AMA Style

Liu C, Bai Z, Cheng J. Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials. Am J Intern Med. 2025;13(4):54-63. doi: 10.11648/j.ajim.20251304.12

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@article{10.11648/j.ajim.20251304.12,
  author = {Can Liu and Zeming Bai and Jingmin Cheng},
  title = {Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials
},
  journal = {American Journal of Internal Medicine},
  volume = {13},
  number = {4},
  pages = {54-63},
  doi = {10.11648/j.ajim.20251304.12},
  url = {https://doi.org/10.11648/j.ajim.20251304.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20251304.12},
  abstract = {Non-alcoholic fatty liver disease (NAFLD) is one of the most common fatty liver diseases, leading to biochemical and histological disorders in NAFLD. It is characterized by kinds of pathologies, ranging from simple non-alcoholic fatty liver (NAFL) to serious non-alcoholic steatohepatitis (NASH) with the complication of steatosis, fibrosis, NASH cirrhosis and hepatocellular carcinoma (HCC). The most important potential risk factors including insulin resistance and increased oxidative stress, especially vitamin E, have significant influence on the treatment for NAFLD. Vitamin E, as a key fat-soluble antioxidant, presents potential therapeutic value in the intervention of NAFLD. At present, there are differences in the intervention measures proposed by various studies, and the efficacy of corresponding intervention measures has not yet reached a unified conclusion. To analyze the relevant research on the combination therapy of vitamin E in NAFLD patients, and to explore the intervention effect of vitamin E combination therapy on their biochemical indicators and histological abnormalities. PubMed, EMBASE, Medline, Cochrane, ScienceDirect, Web of science, and Google Scholar Database were systematically searched to screen studies on the intervention effect of vitamin E combination therapy on NAFLD from January 2005 to April 2025. A total of 9 randomized controlled trials (RCT) were included, which included 885 participants with an average age of 35~48.04 years. The combination therapy of vitamin E had significantly improved liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT)) in NAFLD patients in most studies, and had also positive effects in improving liver histological parameters (NAFLD activity score (NAS), steatosis, fibrosis score, and inflammation), but there was heterogeneity among these studies. In addition, some studies did not observe significant improvement in ballooning, and only one study showed that combination therapy had no significant effect on liver function testing. The combination therapy of vitamin E has potential benefits in improving liver function indicators and some histological parameters in NAFLD patients, but its efficacy varies among studies. In the future, more high-quality and long-term RCT need to be conducted to further clarify the optimal regimen and applicable population of vitamin E in the treatment of NAFLD, providing a more comprehensive and reliable reference for clinical practice.
},
 year = {2025}
}

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TY  - JOUR
T1  - Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials

AU  - Can Liu
AU  - Zeming Bai
AU  - Jingmin Cheng
Y1  - 2025/09/05
PY  - 2025
N1  - https://doi.org/10.11648/j.ajim.20251304.12
DO  - 10.11648/j.ajim.20251304.12
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 54
EP  - 63
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20251304.12
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common fatty liver diseases, leading to biochemical and histological disorders in NAFLD. It is characterized by kinds of pathologies, ranging from simple non-alcoholic fatty liver (NAFL) to serious non-alcoholic steatohepatitis (NASH) with the complication of steatosis, fibrosis, NASH cirrhosis and hepatocellular carcinoma (HCC). The most important potential risk factors including insulin resistance and increased oxidative stress, especially vitamin E, have significant influence on the treatment for NAFLD. Vitamin E, as a key fat-soluble antioxidant, presents potential therapeutic value in the intervention of NAFLD. At present, there are differences in the intervention measures proposed by various studies, and the efficacy of corresponding intervention measures has not yet reached a unified conclusion. To analyze the relevant research on the combination therapy of vitamin E in NAFLD patients, and to explore the intervention effect of vitamin E combination therapy on their biochemical indicators and histological abnormalities. PubMed, EMBASE, Medline, Cochrane, ScienceDirect, Web of science, and Google Scholar Database were systematically searched to screen studies on the intervention effect of vitamin E combination therapy on NAFLD from January 2005 to April 2025. A total of 9 randomized controlled trials (RCT) were included, which included 885 participants with an average age of 35~48.04 years. The combination therapy of vitamin E had significantly improved liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT)) in NAFLD patients in most studies, and had also positive effects in improving liver histological parameters (NAFLD activity score (NAS), steatosis, fibrosis score, and inflammation), but there was heterogeneity among these studies. In addition, some studies did not observe significant improvement in ballooning, and only one study showed that combination therapy had no significant effect on liver function testing. The combination therapy of vitamin E has potential benefits in improving liver function indicators and some histological parameters in NAFLD patients, but its efficacy varies among studies. In the future, more high-quality and long-term RCT need to be conducted to further clarify the optimal regimen and applicable population of vitamin E in the treatment of NAFLD, providing a more comprehensive and reliable reference for clinical practice.

VL  - 13
IS  - 4
ER  -

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Author Information

Can Liu

School of Management, Shanxi Medical University, Taiyuan, China; School of Public Health, Shanxi Medical University, Taiyuan, China

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http://orcid.org/0000-0002-8955-6245
Zeming Bai

School of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China

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http://orcid.org/0009-0004-8518-7202
Jingmin Cheng

School of Management, Shanxi Medical University, Taiyuan, China

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http://orcid.org/0009-0002-8937-9389

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Figure 1

Figure 1. Describes the literature review process.

Plain Text BibTeX RIS

APA Style

Liu, C., Bai, Z., Cheng, J. (2025). Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials. American Journal of Internal Medicine, 13(4), 54-63. https://doi.org/10.11648/j.ajim.20251304.12

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ACS Style

Liu, C.; Bai, Z.; Cheng, J. Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials. Am. J. Intern. Med. 2025, 13(4), 54-63. doi: 10.11648/j.ajim.20251304.12

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AMA Style

Liu C, Bai Z, Cheng J. Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials. Am J Intern Med. 2025;13(4):54-63. doi: 10.11648/j.ajim.20251304.12

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@article{10.11648/j.ajim.20251304.12,
  author = {Can Liu and Zeming Bai and Jingmin Cheng},
  title = {Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials
},
  journal = {American Journal of Internal Medicine},
  volume = {13},
  number = {4},
  pages = {54-63},
  doi = {10.11648/j.ajim.20251304.12},
  url = {https://doi.org/10.11648/j.ajim.20251304.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20251304.12},
  abstract = {Non-alcoholic fatty liver disease (NAFLD) is one of the most common fatty liver diseases, leading to biochemical and histological disorders in NAFLD. It is characterized by kinds of pathologies, ranging from simple non-alcoholic fatty liver (NAFL) to serious non-alcoholic steatohepatitis (NASH) with the complication of steatosis, fibrosis, NASH cirrhosis and hepatocellular carcinoma (HCC). The most important potential risk factors including insulin resistance and increased oxidative stress, especially vitamin E, have significant influence on the treatment for NAFLD. Vitamin E, as a key fat-soluble antioxidant, presents potential therapeutic value in the intervention of NAFLD. At present, there are differences in the intervention measures proposed by various studies, and the efficacy of corresponding intervention measures has not yet reached a unified conclusion. To analyze the relevant research on the combination therapy of vitamin E in NAFLD patients, and to explore the intervention effect of vitamin E combination therapy on their biochemical indicators and histological abnormalities. PubMed, EMBASE, Medline, Cochrane, ScienceDirect, Web of science, and Google Scholar Database were systematically searched to screen studies on the intervention effect of vitamin E combination therapy on NAFLD from January 2005 to April 2025. A total of 9 randomized controlled trials (RCT) were included, which included 885 participants with an average age of 35~48.04 years. The combination therapy of vitamin E had significantly improved liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT)) in NAFLD patients in most studies, and had also positive effects in improving liver histological parameters (NAFLD activity score (NAS), steatosis, fibrosis score, and inflammation), but there was heterogeneity among these studies. In addition, some studies did not observe significant improvement in ballooning, and only one study showed that combination therapy had no significant effect on liver function testing. The combination therapy of vitamin E has potential benefits in improving liver function indicators and some histological parameters in NAFLD patients, but its efficacy varies among studies. In the future, more high-quality and long-term RCT need to be conducted to further clarify the optimal regimen and applicable population of vitamin E in the treatment of NAFLD, providing a more comprehensive and reliable reference for clinical practice.
},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Vitamin E as a Therapeutic Agent for NAFLD: A Systematic Review of Randomized Controlled Trials

AU  - Can Liu
AU  - Zeming Bai
AU  - Jingmin Cheng
Y1  - 2025/09/05
PY  - 2025
N1  - https://doi.org/10.11648/j.ajim.20251304.12
DO  - 10.11648/j.ajim.20251304.12
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 54
EP  - 63
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20251304.12
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common fatty liver diseases, leading to biochemical and histological disorders in NAFLD. It is characterized by kinds of pathologies, ranging from simple non-alcoholic fatty liver (NAFL) to serious non-alcoholic steatohepatitis (NASH) with the complication of steatosis, fibrosis, NASH cirrhosis and hepatocellular carcinoma (HCC). The most important potential risk factors including insulin resistance and increased oxidative stress, especially vitamin E, have significant influence on the treatment for NAFLD. Vitamin E, as a key fat-soluble antioxidant, presents potential therapeutic value in the intervention of NAFLD. At present, there are differences in the intervention measures proposed by various studies, and the efficacy of corresponding intervention measures has not yet reached a unified conclusion. To analyze the relevant research on the combination therapy of vitamin E in NAFLD patients, and to explore the intervention effect of vitamin E combination therapy on their biochemical indicators and histological abnormalities. PubMed, EMBASE, Medline, Cochrane, ScienceDirect, Web of science, and Google Scholar Database were systematically searched to screen studies on the intervention effect of vitamin E combination therapy on NAFLD from January 2005 to April 2025. A total of 9 randomized controlled trials (RCT) were included, which included 885 participants with an average age of 35~48.04 years. The combination therapy of vitamin E had significantly improved liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT)) in NAFLD patients in most studies, and had also positive effects in improving liver histological parameters (NAFLD activity score (NAS), steatosis, fibrosis score, and inflammation), but there was heterogeneity among these studies. In addition, some studies did not observe significant improvement in ballooning, and only one study showed that combination therapy had no significant effect on liver function testing. The combination therapy of vitamin E has potential benefits in improving liver function indicators and some histological parameters in NAFLD patients, but its efficacy varies among studies. In the future, more high-quality and long-term RCT need to be conducted to further clarify the optimal regimen and applicable population of vitamin E in the treatment of NAFLD, providing a more comprehensive and reliable reference for clinical practice.

VL  - 13
IS  - 4
ER  -

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