Cardiovascular Risk Factor
Conditions
Brief summary
Berberine is extracted from Coptis (Huanglian) and Phellodendron Chinese (Huangbai), to make into berberine tablets.1 Recent studies have shown that berberine has beneficial effects on cardiovascular disease (CVD) risk factors,1,2 such as lowering the risk of hyperlipidemia, diabetes, and hypertension.1 In a comprehensive systematic review and meta-analysis of 27 randomized controlled trials (RCTs), berberine effectively reduced low density lipoprotein cholesterol (LDL-c) (-0.65 mmol/L, 95% confidence interval (CI) -0.75 to -0.56), triglycerides (TG) (-0.39 mmol/L, 95% CI -0.59 to -0.19), total cholesterol (TC) (-0.66 mmol/L, 95% CI -1.02 to -0.31) and increased high density lipoprotein cholesterol (HDL-c) (0.07mmol/L, 95% CI 0.04 to 0.1).1 Notably, no serious adverse event has been reported in these trials,1 suggesting a good tolerability of berberine. The mechanism by which berberine exerts a protective role in atherosclerosis is unclear. Protoberberines have been identified as a new inhibitor of AKR1C3, an enzyme responsible for the regulation of steroid hormone action.3 The investigators propose to examine the effects of berberine on a set of well-established CVD risk factors including lipids, systolic and diastolic blood pressure, coagulation factors, adiposity, fasting glucose, insulin, and liver function, as well as to examine potential mediation via testosterone and/or sex hormone binding globulin using a mechanistic, randomized, double-blind, placebo-controlled trial in Chinese men with hyperlipidemia.
Detailed description
Objectives: to assess the effect of berberine on a set of well-established CVD risk factors, including lipids, systolic and diastolic blood pressure, coagulation factors, fasting glucose, insulin, adiposity (body mass index (BMI) and waist-hip ratio (WHR)) and the mediation via testosterone and/or sex hormone binding globulin using a mechanistic, parallel RCT. Study design: a mechanistic, randomized, double-blind, placebo-controlled, parallel trial in 84 Chinese men in Hong Kong. Interventions: the eligible participants will be randomized to take berberine (500 mg orally twice a day) or placebo for 12 weeks. Blood samples will be taken at baseline, 8-week and 12-week intervention. Data analysis and expected results: the investigators will use an intention to treat analysis, with multiple imputation for missing data. The investigators will compare the baseline characteristics of participants in the two arms using analysis of variance. The investigators will assess the effects of berberine on changes in CVD risk factors using analysis of variance, and the mediation using causal mediation analysis. Compared to the placebo group, the participants receiving berberine are expected to have lower burden of cardiovascular disease risk factors at the end of the intervention. These effects may be mediated or partly mediated by lowering testosterone.
Interventions
DRUGBerberine
Purified berberine (500 mg orally twice a day) in tablets for 12 weeks
DRUGPlacebo
Placebo tablets, prepared with the same appearance, for 12 weeks
Sponsors
Food and Health Bureau, Hong Kong
The University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men, who are 1. aged 20 to 65 years 2. of Chinese ethnicity 3. with hyperlipidemia, defined as TG greater than 150 mg/dl (1.70 mmol/L), TC greater than 200 mg/dl (5.16 mmol/L), and/or LDL-c greater than 100 mg/dl (2.58 mmol/L) 4. willing to make return visits 5. not currently receiving hormone replacement therapy, such as testosterone replacement therapy, in the past 12 months 6. not currently taking berberine or traditional Chinese medicine that contains berberine, in the past 1 month 7. free of any congenital diseases, including familial hypercholesterolemia 8. free of any infectious diseases, e.g. seasonal influenza 9. free of anemia and glucose-6-phosphate dehydrogenase deficiency 10. with no history of any chronic diseases including ischemic heart disease, myocardial infarction (heart attack), stroke, diabetes, cancer, liver/renal dysfunction, and gastrointestinal disorders.
Exclusion criteria
* All women, and men, who did not meet the aforementioned inclusion criteria, and/or unable or unwilling to provide consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| lipid profile | change from baseline lipid profile at 8 weeks | LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L |
| blood pressure | change from baseline blood pressure at 8 weeks | systolic blood pressure and diastolic blood pressure in mmHg |
| thromboxane A2 | change from baseline thromboxane A2 at 8 weeks | thromboxane A2 in mmol/L |
| testosterone | change from baseline testosterone at 8 weeks | testosterone in mmol/L |
| body mass index (BMI) | change from baseline body mass index at 8 weeks | weight and height will be combined to report BMI in kg/m\^2 |
| waist hip ratio | change from baseline waist hip ratio at 8 weeks | waist circumstance and hip circumstance will be combined to report waist hip ratio |
| fasting glucose | change from baseline fasting glucose at 8 weeks | fasting glucose in mmol/L |
| fasting insulin | change from baseline fasting insulin at 8 weeks | fasting insulin in mmol/L |
| liver function | change from baseline fasting insulin at 8 weeks | Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L |
| sex hormone binding globulin (SHBG) | change from baseline SHBG at 8 weeks | SHBG in nmol/L |
| thrombin time | change from baseline thrombin time at 8 weeks | thrombin time in sec |
Countries
Hong Kong
Outcome results
None listed