Curcumin, Antioxidant, and Pioglitazone Therapy with Inclusion of Vitamin E In Non-Alcoholic Fatty Liver Disease: A Randomized, Open-label, Placebo-controlled Clinical Prospective Trial (CAPTIVE)

Abstract

Purpose: NAFLD is a global clinical challenge which progresses to cirrhosis and liver cancer. Defective transport of free fatty acids and mitochondrial dysfunction lead to explosion of a series of free radicals, apoptosis, up regulated cytokines, and fibrogenesis, ultimately causing cirrhosis and cancer. Curcumin is a pan-antioxidant with anti-inflammatory, anti-apoptotic, anti-microbial, and anti-fibrogenic properties. This study evaluates the role of curcumin in NAFLD to progression of NASH. Methods: Eighty patients (n=80) with mean BMI 29% were recruited, NAFLD score 0.66, NASH fibrotic score 0.33, HOMA IR 3.8, ALT 58, LDLc 143, HDLc 29, triglyceride 186, and adipokines (leptin, adiponectin, retinal binding proteins) were divided into Group A - (n=20) pioglitazone 15 mg; Group B - (n=20) vitamin E; Group C - (n=20) curcumin (all the three above groups received placebo); and Group D - (n=20) vitamin E plus curcumin. Pre and post values (triglycerides, LDLc, HDLc, ALT, HOMA-IR, TNF-alfa, leptin, adiponectin, retinol binding protein, HBA1c, serum necro-inflammatory NAFLD, and NASH fibrotic score were analyzed at 3, 6, and 12 months. Diet and exercise were left unchanged. Daily alcohol content was less than 30 grams. Exclusion: HIV, medications causing fatty liver, including herbal supplements, lipodystropy, overt diabetes mellitus, pregnancy, and hypersensitivity to study medications. Results: Group A: Minimal changes on ALT, HbA1c, HOMA, lipids; no changes in TNF-alfa, adipokines, lipid profile, and necro-inflammatory score and/or NASH fibrosis score. Group B and Group C had modest changes in ALT, lipid profile, HbA1c, and HOMA, while no changes in adipokines, necro-inflammatory score, and fibrotic score. Group D had significant changes in all scores, particularly the adipokines, and small improvements in fibrotic score. All patients tolerated the medications well. Conclusion: This study postulates the positive effects of curcumin added to vitamin E in NAFLD subgroups, even preventing NASH with a modest anti-fibrotic effect, improved necroinflammatory score, and impressive changes in adipokines levels. Additive effects of curcumin with vitamin E has significant effects on serum lipids and insulin sensitivity. Unavailability of pre- and post-liver biopsy was the limitation of this study. A large control trial needs to validate.