Effects of Tablets of Silybum Marianum, Pueraria Lobate and Salvia Miltiorrhiza on Fatty Liver

Effects of Tablets of Silybum Marianum, Pueraria Lobate and Salvia Miltiorrhiza on the Progression of Fatty Liver in Adults: a Double-blinded Randomized Placebo-controlled Clinical Trial

Objectives: To examine the effects of tablets of silybum marianum, Pueraria lobate and salvia miltiorrhiza on the progression of fatty liver in patients with fatty liver. Design: a double-blinded randomized placebo-controlled clinical trial. Setting: community residents, Guangzhou city, South China. Participants: a total 118 men and women (18-65 years), with BMI range of 24-30 kg/m2, and with fatty liver screened by ultrasound or MR at baseline. Arms and Interventions: 118 participants were randomly allocated into two arms using a block randomization method. Experimental Arm: tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza, 3 tablets (1g each) twice a day for 6 months; Placebo Arm: placebo tablets, 3 tablets (1g each) twice a day for 6 months. Outcome Measures: determined at baseline and at 6 months post treatment Primary Outcome Measures: 1) proton density fat fraction of liver assessed by MR; 2) serum liver fibrosis biomarkers: type procollagen III N terminal peptide, hyaluronic acid, laminin, collagen type IV, and glycocholic acid; 3) NAFLD fibrosis score. Secondary Outcome Measures: 1) serum liver function biomarkers: AST, ALT, GGT, ALP, total protein, and bile acids; 2) fasting blood lipids: total triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol; 3) fasting serum glucose and insulin; 4) serum inflammatory factors (hsCRP and IL-6); 5) oxidative stress: SOD and MDA; and 6) body measurements and body fat mass. Data Analyses: Mean changes in the above outcome measures from baseline to 6 months will be compared between the two arms.

Placebo with the same appearance, taste, smell, and packing box to the experimental supplement was used. 118 serial numbers matched to each one participant, and corresponding to study arms (named as 1 or 2 on the tablet box), were used to replace the original label of supplement or placebo after randomization. The code of serial number corresponding to the group code (1 or 2) of tablets was kept by the PI, and will not be disclosed until the completion of all data collection. The group code corresponding to the two types of tablets was/will be kept by the producer till the completion of data analysis.

Tablet name: tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza; Dosage: 1g/tablet, 3 tablets/time； Frequency: 2 times/day; Duration: 6 months

Tablet name: Placebo; Dosage: 1g/tablet, 3 tablets/time； Frequency: 2 times/day; Duration: 6 months

Brand names: BY-HEALTH； Main contents (per 100g): silibinin 2g, salvianolic acid B 0.72g，Puerarin 0.68g

NAFLD fibrosis score: = -1.675 + 0.037 Age (yrs) + 0.094 BMI (kg/m2) + 1.13 impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 AST/ALT ratio - 0.013Platelet (*10E9/L) - 0.66 Albumin (g/dl)

Fat mass (FM): FM (kg) at total body and sub-regions determined by a dual energy x-ray absorptiometry (DXA)

Anxiety Score: assessed by a Self Rating Anxiety Scale (SAS).the minimum and maximum values: 25-100 points. Higher scores mean worse outcome.

Inclusion Criteria: Age: 18-65 years BMI: 24-30 kg/m2 Fatty liver, assessed by ultrasound or MR Had normal diet and normal daily life. Exclusion Criteria: Hospital confirmed diseases of heart, liver (viral hepatitis, drug-induced liver injury, cirrhosis), kidney, brain, hematopoietic system，diabetes, immune system, and cancer； Taking medicine or supplements known to affect fatty liver, body fat; Body weight had changed more than 10% within the past 3 months; Physical or mental disabled to participate the trial; Compliance of tablet consumption is/was less than 80% in run-in period; Pregnant or lactating women, or intended pregnancy during the trial period; Be allergic to the proposed supplements； Attended or plan to attend other trial(s); Be unwell to sign the informed consent form, or have other conditions that be not suitable to attend the trial considered by the investigators.