Table 3.
Summary of clinical studies in DDB
| Study | Etiology | Inclusion criteria | Intervention period | Arms (n) | Age (years) | Outcomes | Study design |
|---|---|---|---|---|---|---|---|
| Lee et al. [10] (2014) | CLD | (1) Persistent ALT ≥1.5×ULN more than once during the previous 6 months; (2) ALT ≥1.5×ULN at enrollment | 24 weeks | DDB 750 mg/day (67) | 51 (20–72) | ALT normalization (≤40 IU/L) (80.0% vs. 34.8%; P<0.001) | RCT; double blind, active- controlled |
| Kang et al. [108] (2001) | CLD | (1) Biopsy-proven chronic hepatitis or (2) abnormal AST/ALT for >6 months; no evidence of viral hepatitis B or C | 8 weeks | High-dose group: DDB 150 mg + carnitine/orotate complex 900 mg/day (33) | 49.03±9.74 | ALT normalization (88.5% vs. 54.6% vs.44.4%; P=0.0027) | RCT; double blind, phase II |
| Low-dose group: DDB 150 mg + carnitine/orotate complex 600 mg/day (30) | 41.58±11.73 | ||||||
| DDB 150 mg/day (32) | 44.00±11.55 | ||||||
| Park et al. [109] (2001) | CLD | (1) Biopsy- proven chronic hepatitis or (2) ALT elevation (≥1.5×ULN) more than twice during the previous 6 months; no evidence of viral hepatitis B or C | 8 weeks | High-dose group: DDB 150 mg + carnitine/orotate complex 900 mg/day (53) | 44.57±11.49 | ALT normalization (81.13% vs. 67.35% vs. 64.54%; P=0.0407) | RCT; double blind, phase III |
| Low-dose group: DDB 100 mg + carnitine/orotate complex 600 mg/day (48) | 43.24±13.01 | ||||||
| DDB 100 mg/day (52) | 45.63±13.75 | ||||||
| Kim et al. [110] (2014) | CLD | (1) Abnormal ALT or AST in previous 6 months, (2) sonographical findings of chronic hepatitis or fatty liver, or (3) history of being treated for chronic hepatitis for >30 days | 12 weeks | DDB + garlic oil 960 mg/day (100) | 44 (20–79) | ALT normalization (≤40 IU/L) (89% vs. 18.6% vs. 22.9%; P<0.001) | RCT;double blind, placebo- andactive- controlled, phaseIV |
| Silymarin 1,018 mg/day (102) | 49 (20–75) | ||||||
| Placebo (35) | 44 (24–77) | ||||||
| Hong et al. [111] (2014) | NAFLD | Combined with impaired fasting glucose metabolism | 12 weeks | Metformin 750 mg/day and DDB-carnitine orotate complex 900 mg/day (26) | 51.5±9.4 | Decrement of ALT level (mean, 51.5 vs. 16.7; P=0.001) | RCT; double blind, placebo- controlled |
| Metformin 750 mg/day and placebo (26) | 52.0±9.6 | ||||||
| Bae et al. [112] (2015) | NAFLD | Combined with type 2 diabetes | 12 weeks | DDB-carnitine orotate complex 824 mg/day (39) | 50.6±9.3 | ALT normalization (<30 IU/L in men or <19 IU/L in women) (89.7% vs. 17.9%; P<0.001) | RCT; double blind, placebo- controlled |
| Placebo (39) | 52.0±9.4 | ||||||
| Jun et al. [113] (2013) | HBV | (1) ALT ≥80 IU/L, (2) ALT < ULN×10, (3) treatment- naïve, and (4) HBV >105 copies/ mL in case of HBeAg-positive result or HBV >104 copies/ mL in case of HBeAg-negative result | 12 months | Entecavir 0.5 mg/day and DDB- carnitine orotate 2,472 mg/ day complex (67) | 43.0 ± 9.8 | ALT normalization (<40 U/L) (100% vs. 85.7%; P=0.0019) | RCT |
| Entecavir 0.5 mg/day (63) | 44.9±10.0 |
Variables are expressed as median (interquartile range) or mean±standard deviation.
DDB, dimethyl-4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate; CLD, chronic liver disease; ALT, alanine aminotransferase; ULN, upper limit of normal; RCT, randomized controlled trial; AST, aspartate aminotransferase; NAFLD, nonalcoholic fatty liver disease; HBV, hepatitis virus; HBeAg, hepatitis B e antigen.