Table 7.
Summary of clinical studies in vitamin E
| Study | Etiology | Inclusion criteria | Intervention period | Arms (n) | Age (years) | Outcomes | Study design |
|---|---|---|---|---|---|---|---|
| Harrison et al. [233] (2003) | NAFLD | Histologic diagnosis of NASH | 6 months | Vitamin E 1,000 IU/day and C 1,000 mg/day (23) | 50.2 | · Improvement in fibrosis score (47.8% vs. 40.9%; P=0.005) | RCT |
| Placebo (22) | 52.5 | · No changes in inflammation (P>0.05) | |||||
| · ALT improvement (P=0.007) | |||||||
| Sanyal et al. [279] (2004) | NAFLD | Non-diabetic, non-cirrhotic | 6 months | Vitamin E 400 IU/day (10) | 46±13 | · Vitamin E: Improvement in steatosis (P=0.02), ballooning (P=0.055) and portal fibrosis (P>0.05) | RCT |
| Vitamin E 400 IU/day + pioglitazone 30 mg/day (10) | 47±12 | · Vitamin E + pioglitazone: Improvement in steatosis (P=0.002), ballooning (P=0.01), and portal fibrosis (P>0.05) | |||||
| · Comparison between the two groups: steatosis (P<0.05), ballooning (P>0.05), portal fibrosis (P>0.05) | |||||||
| Ersöz et al. [280] (2005) | NAFLD | Histologically proven NAFLD | 6 months | Vitamin E 600 IU/day and C 500 mg/day (28) | 46.3±9.4 | · ALT change (IU/L) (mean, 91.9 to 39.1, P<0.05 vs. 93.7 to 49.1, P<0.05; P>0.05) | Open-label RCT |
| UDCA 10 mg/kg/day (29) | 47.9±10.6 | ||||||
| Dufour et al. [54] (2006) | NAFLD | Histologic diagnosis of NASH | 6 months | UDCA 12–15 mg/kg/day + vitamin E 800 IU/day (15) | 46±14 | · Decrease in AST and ALT levels (IU/L) (UDCA + vitamin E vs. placebo, P<0.05; UDCA vs. placebo, P>0.05) | Double-blinded RCT |
| UDCA 12–15 mg/kg/day + placebo (18) | 47±12 | · Improvement in steatosis (UDCA + vitamin E vs. placebo, P<0.05; UDCA vs. placebo, P>0.05) | |||||
| Placebo + placebo (15) | 44±14 | · No improvement in inflammation and fibrosis (P>0.05) | |||||
| Balmer et al. [55] (2009) | NAFLD | Histologic diagnosis of NAFLD | 2 years | UDCA 12–15 mg/kg/day + vitamin E 800 IU/day (14) | 47±14 | · Adiponectin level change (ng/mL) (mean, +3,808 vs. -1,626 vs. -687; P<0.03) | Double-blinded RCT |
| UDCA 12–15 mg/kg/day + placebo (14) | 47±12 | ||||||
| Placebo + placebo (13) | 46±13 | ||||||
| Sanyal et al. [14] (2010) | NAFLD | Histologic diagnosis of NASH without diabetes | 96 weeks | Pioglitazone 30 mg/day (80) | 47.0±12.6 | · Improvement in NASH (vitamin E 43% vs. placebo 19%, P=0.001; pioglitazone 34% vs. placebo 19%, P=0.04) | Double-blinded RCT |
| Vitamin E 800 IU/day (84) | 46.6±12.1 | · Improvement in fibrosis (vitamin E 41% vs. placebo 31%, P=0.24; pioglitazone 44% vs. placebo 31%, P=0.12) | |||||
| Placebo (83) | 45.4±11.2 | · Changes in serum aminotransferase level (IU/L) (mean, vitamin E -37.0 vs. placebo -20.1, P=0.001; pioglitazone -40.8 vs. placebo -20.1, P<0.001) | |||||
| Aller et al. [232] (2015) | NAFLD | Histologic diagnosis of NAFLD | 3 months | Silymarin 1,080.6 mg/day + vitamin E 72 mg/day (18) | 47.4±11.2 | · Decrease in fatty liver index (mean, 86.2 to 76.9; P<0.05 vs. 85.2 to 77.5; P<0.05) | RCT |
| Control (18) | 43.75±3.5 | · Decrease in NFS (mean, -1.6 to -2.1; P<0.05 vs. -1.0 to -1.5; P<0.05) | |||||
| Parikh et al. [34] (2016) | NAFLD | Non-diabetic, non-cirrhotic | 52 weeks | Vitamin E 800 IU/day (100) | 40.19±2.9 | · ALT normalization (14% vs. 19%; P=0.2) | Open-label RCT |
| UDCA 600 mg/day (150) | · ALT reduction (56% vs. 63%; P=0.2) | ||||||
| Polyzos et al. [229] (2017) | NAFLD | Histologic diagnosis of NASH | 52 weeks | Vitamin E 800 IU/day + spironolactone 25 mg/day (14) | 54.9±1.8 | · NFS reduction (44% vs. 47%; P=0.69) | Open-label RCT |
| Vitamin E 800 IU/day (17) | 53.8±3.4 | · ALT reduction (IU/L) (43.5 to 40.0, P>0.05 vs. 66.0 to 42.1, P>0.05; P>0.05) | |||||
| Bril et al. [237] (2019) | NAFLD | Histologic diagnosis of NASH and type 2 diabetes | 18 months | Vitamin E 800 IU/day (36) | 60±9 | · NAFLD liver fat score reduction (P=0.028 vs. P=0.61) | Double-blinded RCT |
| Vitamin E 800 IU/day + pioglitazone 30-45 mg/day (37) | 60±6 | · Reduction of NAS (vitamin E 31% vs. placebo 19%, P=0.26; vitamin E + pioglitazone 54% vs. placebo 19%, P=0.003) | |||||
| Placebo (32) | 57±11 | · Resolution of NASH (vitamin E 33% vs. placebo 12%, P=0.04; vitamin E + pioglitazone 43% vs. placebo 12%, P=0.005) | |||||
| Fouda et al. [227] (2021) | NAFLD | Histologic diagnosis of NASH | 3 months | Vitamin E 800 IU/day (34) | 44.8±9.7 | · Fibrosis change (vitamin E 50% vs. placebo 30%, P=0.09; vitamin E + pioglitazone 52% vs. placebo 30%, P=0.07) | Single-blind RCT |
| UDCA 500 mg/day (34) | 43.4±11 | · ALT reduction (P<0.05) | |||||
| Pentoxifylline 800 mg/day (34) | 45.2±11 | · Inflammatory cytokine reduction (IL-6, CCL-2/MCP-1) (P<0.05) | |||||
| Kedarisetty et al. [228] (2021) | NAFLD | Histologic diagnosis of NASH | 1 year | Vitamin E 800 IU/day (33) | 35 (16–64) | · ALT reduction (IU/L) (mean 85.5 to 28 vs. 97 to 24; P=0.23) | Open-label RCT |
| Vitamin E 800 IU/day + pentoxifylline 1,200 mg/day (36) | 40 (20–64) | · NAS change (mean 4.3 to 3.1 vs. 5 to 2.8; P=0.45) | |||||
| · Fibrosis stage change (mean 1.7 to 1.7 vs. 2.1 to 1.0; P=0.004) | |||||||
| · Insulin change (mU/L) (mean 12.4 to 10.8 vs. 12.9 to 7.6; P=0.048) | |||||||
| · TNF-α change (pg/mL) (mean 7.14 to 3.83 vs. 7.85 to 1.59; P=0.001) | |||||||
| Groenbaek et al. [248] (2006) | HCV | Elevated ALT | 6 months | Vitamin C 500 mg/day + vitamin E 945 IU/day + selenium 200 µg/day (12) | 45 (33–53) | · Change in serum ALT (IU/L) (mean, -8 vs. -6; P=0.60) | Double-blinded RCT |
| Placebo (11) | 45 (23–55) | · Change in HCV RNA (log10 eqv/L) (mean, 0.17 vs. 0.41; P=0.24) | |||||
| Marotta et al. [246] (2007) | HCV | Cirrhosis, genotype 1, and elevated ALT | 6 months | Vitamin E 900 IU/day (25) | 62 (54–75) | · Improvement of redox status, GSH, GSSG, GSH/GSSG and MDA: vitamin E (P<0.05) and FPP (P<0.05) | RCT |
| Fermented papaya preparation 9 g/day (25) | |||||||
| Control (10) | |||||||
| Bunchorntavakul et al. [249] (2014) | HCV | Genotype 3 | 12 weeks | Vitamin E 800 IU/day (19) | 48.8±8.3 | · Decrease in serum ALT (mean, 105.1 to 96.5; P=0.260 vs. 107.5 to 120.4) | Double- blinded RCT |
| Placebo (18) | 49.5±8.6 | · ALT responder (57.8% vs. 29.4%; P=0.106) | |||||
| Malaguarnera et al. [245] (2015) | HCV | Received PegIFN- α2b + ribavirin | 12 months | Silybin 47 mg/day + vitamin E 15 mg/day + phospholipid 97 mg/day (32) | 46.4±6.9 | · Decrease in ALT level (IU/L) (mean, 170.2 to 36.9, P<0.001 vs. 161.6 to 69.2, P<0.001; P<0.001) | Double- blinded RCT |
| · Decrease in viremia (106 IU/mL) (mean, 5.32 to 1.67, P<0.05 vs. 5.4 to 3.24, P<0.001; P<0.05) | |||||||
| Placebo (32) | 45.2±6.7 | · Decrease in TGF-β (ng/mL) (mean, 54.2 to 32.8, P<0.05 vs. 51.8 to 45.2, P<0.05; P<0.05) | |||||
| · Decrease in PIIINP (ng/mL) (mean, 43.8 to 33.4, P<0.001 vs. 44.7 to 39.8, P<0.05; P<0.05) | |||||||
| · Decrease in TIMP-1 (ng/mL) (mean, 480.2 to 310.6, P<0.001 vs. 487.2 to 421.0, P<0.001; P<0.001) | |||||||
| Andreone et al. [251] (2001) | HBV | Positive HBV DNA and raised ALT (1.5×ULN) | 3 months | Vitamin E 600 IU/day (15) | 37±15 | · ALT normalization (47% vs. 6%; P=0.011) | RCT |
| Control (17) | 42±14 | · Negative HBV DNA (53% and 18%; P=0.039) | |||||
| · Complete response (47% vs. 0%; P=0.0019) |
Variables are expressed as median (interquartile range) or mean±standard deviation.
NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; ALT, alanine aminotransferase; RCT, randomized controlled trial; UDCA, ursodeoxycholic acid; AST, aspartate aminotransferase; NFS, NAFLD fibrosis score; IL-6, interleukin-6; CCL2, C-C motif ligand 2; MCP, monocyte chemoattractant protein; NAS, NAFLD activity score; TNF, tumor necrosis factor; HCV, hepatitis C virus; GSH, glutathione; GSSG, glutathione disulfide, MDA, malondialdehyde; FPP, fermented papaya preparation; PegIFN, pegylated interferon; TGF, transforming growth factor; PIIINP, pro-collagen III N-terminal peptide; TIMP, tissue inhibitor of metalloproteinase; HBV, hepatitis B virus; ULN, upper limit of normal.