Non-alcoholic Fatty Liver Disease
Conditions
Keywords
Phytosterols, Endothelial progenitor cells
Brief summary
Phytosterols are plant sterols . Phytosterols have anti-inflammation effect. Investigators have a hypothesis: phytosterols reduce oxidative stress , enhance Insulin-like growth factor-1(IGF-1) and endothelial progenitor cells(EPCs). Therefore, phytosterols has novel role in cardiovascular protection.
Detailed description
Fatty liver is the hepatic feature of metabolic syndrome. Metabolic syndrome increase the risk of atherosclerosis and cardiovascular disease. Adipose tissue secrete adipocytes accumulate in the liver result in fatty liver. Excess fat become low density lipoprotein-cholesterol(LDL-C) from liver. Oxidized- LDL-C adherence in the vessel result in atherosclerosis via inflammation and immune response. Phytosterols are present in the nuts, plant oil, broccoli and so on. The structure of phytosterols are similar with cholesterols. After the competition, the smaller absorption of cholesterols. Studies showed the average consumptions of phytosterols were 200mg daily but the enough amount for cardiovascular protection of phytosterols were 2000mg daily. Daily 2000mg phytosterols inhibit the absorption of intestine, reduce the LDL-C about 7-10%. Besides, phytosterols have the effect of anti-inflammation and anti-immune response. The anti-inflammation effect obvious inhibit the monocyte to transform to macrophage, inhibit the formation of foam cell. Clinical studies divided into two groups: 20/20 patients and 4 weeks follow up with cross-over test.First group A: Phytosterols 1800mg/day for 4 weeks ,washout 2 weeks, then placebo 4 weeks. Another group B: placebo 4 weeks, washout 2 weeks, then phytosterols 4 weeks.Cross-over, double blind study was designed. Investigators check the possible benefits of LDL-C, Total -cholesterol,anti-oxidant capacity,C reactive protein,insulin-like growth factor-1, endothelial progenitor cells ; the possible side effect including liver function,muscle enzyme .
Interventions
DIETARY_SUPPLEMENTPhytosterols & placebo
Group A:Phytosterols 1.8g/day with one meal for 4 weeks first;group B:placebo first
Sponsors
China Medical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* (1)25-80 years * (2)Fatty liver was diagnosed by abdominal echo by the same gastrologist, review by another gastrologist
Exclusion criteria
* (1)Serological markers of hepatitis B virus(hepatitis B surface antigen and anti-HBs antibody) and hepatitis C virus infection (anti-HCV antibody) * (2)Autoimmune liver disease or alcoholic liver disease(alcohol intake more than 20g per day by using a questionnaire) * (3)Malignant diseases * (4)Pregnancy or breast feeding * (5)Clinical evidence of angina, congestive heart failure, valvular heart disease, inflammatory disease or thyroid dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | after 4 weeks phytosterols 1.8g/day | Check serum Insulin-like growth factor-1 levels. Serum Insulin-like growth factor-1 (IGF-1) influence metabolic status and reduce EPCs apoptosis via IGF-1 receptor. Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols) |
| Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | after 4 weeks phytosterols 1.8g/day | 1. Check serum metabolic status: levels in total cholesterol, low density lipoprotein-cholesterol, fasting glucose 2. Check serum anti-inflammatory status: levels in C reactive protein Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols) |
| Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | after 4 weeks phytosterols 1.8g/day | Check serum anti-oxidative capacity, especially the serum superoxide dismutase (SOD) levels.Serum SOD provide the anti-oxidative capacity in lipid oxidation. Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols) |
| Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | after 4 weeks phytosterols 1.8g/day | Ceck serum endothelial progenitor cells in the monocytes group but not in the lymphocytes group. Serum EPCs in the monocytes group provide the effect of endothelial repair to support novel vessel protection. Cytometry flow check 150,000 cells per time including monocytes and lymphocytes group. Positive cells is the EPCs in the monocytes group. Stain with KDR, call kinase insert domain receptor, also call as VEGF receptor-2. Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols) |
Countries
Taiwan
Participant flow
Recruitment details
Study from Oct. to Dec.2012 in China Medical University Hospital -Taipei branch Initially,51 patients screened .Finally, 40 patients were enrolled.
Pre-assignment details
Statins, red yeast rice, omega-3 ,fibrates were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Group A:Phytosterols-placebo Daily 1.8g phytosterols powder for 4 weeks, washout 2weeks, then placebo for 4 weeks | 20 |
| Group B:Placebo-phytosterols Placebo for 4 weeks, washout 2 weeks, then daily 1.8g phytosterols powder for 4 weeks | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Group B:Placebo-phytosterols | Group A:Phytosterols-placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 19 Participants | 37 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 18 | 51 years STANDARD_DEVIATION 12 | 51 years STANDARD_DEVIATION 12 |
| Region of Enrollment Taiwan | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease
Check serum anti-oxidative capacity, especially the serum superoxide dismutase (SOD) levels.Serum SOD provide the anti-oxidative capacity in lipid oxidation. Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols)
Time frame: after 4 weeks phytosterols 1.8g/day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A:Phytosterols-placebo | Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | Serum SOD (baseline) | 97.33 U/mg-protein | Standard Error 2.67 |
| Group A:Phytosterols-placebo | Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | Serum SOD (mid-point) | 104.91 U/mg-protein | Standard Error 3.16 |
| Group A:Phytosterols-placebo | Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | Serum SOD (end-point) | 103.28 U/mg-protein | Standard Error 4.18 |
| Group B:Placebo-phytosterols | Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | Serum SOD (baseline) | 99.41 U/mg-protein | Standard Error 2.39 |
| Group B:Placebo-phytosterols | Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | Serum SOD (mid-point) | 95.1 U/mg-protein | Standard Error 2.82 |
| Group B:Placebo-phytosterols | Anti-oxidative Capacity of Phytosterols on Patients With Fatty Liver Disease | Serum SOD (end-point) | 106.54 U/mg-protein | Standard Error 3.76 |
Comparison: Hypothesis: phytosterols increase the anti-oxidative capacity.p-value: <0.05t-test, 1 sided
Primary
Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease
Ceck serum endothelial progenitor cells in the monocytes group but not in the lymphocytes group. Serum EPCs in the monocytes group provide the effect of endothelial repair to support novel vessel protection. Cytometry flow check 150,000 cells per time including monocytes and lymphocytes group. Positive cells is the EPCs in the monocytes group. Stain with KDR, call kinase insert domain receptor, also call as VEGF receptor-2. Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols)
Time frame: after 4 weeks phytosterols 1.8g/day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+ (mid-point) | 23.35 positive cells/150,000 cells | Standard Error 4.88 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+,KDR+ (end-point) | 2.05 positive cells/150,000 cells | Standard Error 0.23 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+,KDR+ (baseline) | 0.9 positive cells/150,000 cells | Standard Error 0.26 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with KDR+,CD133+ (baseline) | 0.8 positive cells/150,000 cells | Standard Error 0.24 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+ (end-point) | 18.7 positive cells/150,000 cells | Standard Error 2.31 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with KDR+,CD133+ (mid-point) | 2.45 positive cells/150,000 cells | Standard Error 0.31 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+,KDR+ (mid-point) | 2.5 positive cells/150,000 cells | Standard Error 0.34 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with KDR+,CD133+ (end-point) | 1.9 positive cells/150,000 cells | Standard Error 0.26 |
| Group A:Phytosterols-placebo | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+ (baseline) | 13.5 positive cells/150,000 cells | Standard Error 2.38 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with KDR+,CD133+ (end-point) | 2.4 positive cells/150,000 cells | Standard Error 0.42 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+ (baseline) | 18.4 positive cells/150,000 cells | Standard Error 2.58 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+ (mid-point) | 18.4 positive cells/150,000 cells | Standard Error 3.74 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+ (end-point) | 28.25 positive cells/150,000 cells | Standard Error 3.68 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+,KDR+ (baseline) | 1.2 positive cells/150,000 cells | Standard Error 0.31 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+,KDR+ (mid-point) | 1.1 positive cells/150,000 cells | Standard Error 0.16 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with CD34+,KDR+ (end-point) | 2.5 positive cells/150,000 cells | Standard Error 0.4 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with KDR+,CD133+ (baseline) | 1.1 positive cells/150,000 cells | Standard Error 0.3 |
| Group B:Placebo-phytosterols | Endothelial Protective Effect of Phytosterols on Patients With Non-alcoholic Fatty Liver Disease | EPCs with KDR+,CD133+ (mid-point) | 1.1 positive cells/150,000 cells | Standard Error 0.16 |
Comparison: Hypothesis:phytosterols increase endothelial progenitor cells to provide endothelial repair and vessel protectionp-value: <0.05t-test, 1 sided
Primary
Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease
Check serum Insulin-like growth factor-1 levels. Serum Insulin-like growth factor-1 (IGF-1) influence metabolic status and reduce EPCs apoptosis via IGF-1 receptor. Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols)
Time frame: after 4 weeks phytosterols 1.8g/day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A:Phytosterols-placebo | Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | Serum IGF-1 (baseline) | 137.14 ng/ml | Standard Error 8.36 |
| Group A:Phytosterols-placebo | Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | Serum IGF-1 (mid-point) | 167.96 ng/ml | Standard Error 9.42 |
| Group A:Phytosterols-placebo | Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | Serum IGF-1 (end-point) | 165.23 ng/ml | Standard Error 7.78 |
| Group B:Placebo-phytosterols | Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | Serum IGF-1 (baseline) | 153.30 ng/ml | Standard Error 10.44 |
| Group B:Placebo-phytosterols | Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | Serum IGF-1 (mid-point) | 150.26 ng/ml | Standard Error 9.37 |
| Group B:Placebo-phytosterols | Insulin-like Growth Factor-1 Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | Serum IGF-1 (end-point) | 178.04 ng/ml | Standard Error 10.88 |
Comparison: Phytosterols increase IGF-1p-value: <0.05t-test, 1 sided
Primary
Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease
1. Check serum metabolic status: levels in total cholesterol, low density lipoprotein-cholesterol, fasting glucose 2. Check serum anti-inflammatory status: levels in C reactive protein Mid-point: end of first intervention (Group A: after phytosterols, Group B: after placebo) End-point: end of second intervention (Group A: after placebo, Group B: after phytosterols)
Time frame: after 4 weeks phytosterols 1.8g/day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | total cholesterol (baseline) | 184.1 mg/dl | Standard Error 6.54 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | total cholesterol (mid-point) | 174.60 mg/dl | Standard Error 6.13 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | total cholesterol (end-point) | 180.55 mg/dl | Standard Error 5.59 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | low density lipoprotein (baseline) | 110.33 mg/dl | Standard Error 6.19 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | low density lipoprotein (mid-point) | 100.76 mg/dl | Standard Error 5.96 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | low density lipoprotein (end-point) | 107.54 mg/dl | Standard Error 5.05 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | fating glucose (baseline) | 106.23 mg/dl | Standard Error 2.4 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | fasting glucose (mid-point) | 100.78 mg/dl | Standard Error 1.88 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | fasting glucose (end-point) | 105.44 mg/dl | Standard Error 2.36 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | c reactive protein (baseline) | 0.32 mg/dl | Standard Error 0.07 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | c reactive protein (mid-point) | 0.23 mg/dl | Standard Error 0.03 |
| Group A:Phytosterols-placebo | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | C reactive protein (end-point) | 0.23 mg/dl | Standard Error 0.03 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | c reactive protein (mid-point) | 0.26 mg/dl | Standard Error 0.04 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | total cholesterol (baseline) | 191.65 mg/dl | Standard Error 8.74 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | fating glucose (baseline) | 105.01 mg/dl | Standard Error 1.8 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | total cholesterol (mid-point) | 199.25 mg/dl | Standard Error 6.7 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | c reactive protein (baseline) | 0.24 mg/dl | Standard Error 0.05 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | total cholesterol (end-point) | 188.60 mg/dl | Standard Error 6.03 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | fasting glucose (mid-point) | 104.88 mg/dl | Standard Error 2.04 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | low density lipoprotein (baseline) | 118.45 mg/dl | Standard Error 7.86 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | C reactive protein (end-point) | 0.19 mg/dl | Standard Error 0.02 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | low density lipoprotein (mid-point) | 121.29 mg/dl | Standard Error 6.1 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | fasting glucose (end-point) | 101.65 mg/dl | Standard Error 1.57 |
| Group B:Placebo-phytosterols | Metabolic Effect of Phytosterols on Patients With Nonalcoholic Fatty Liver Disease | low density lipoprotein (end-point) | 112.66 mg/dl | Standard Error 5.46 |
Comparison: Hypothesis: phytosterols improve metabolic statusp-value: <0.05t-test, 1 sided