OBJECTIVES: Evidences from randomized clinical trials and meta-analysis have claimed an association between the use of soluble dietary fiber from psyllium and a cholesterol-lowering effect. However, there is still uncertainty as to the dose-response relationship and its long-term lipid-lowering efficacy. This meta-analysis was primarily conducted to address the dose-response relationship between psyllium and serum cholesterol level and time-dependent effect of psyllium in mild-to-moderate hypercholesterolemic subjects. METHODS: Twenty-one studies, which enrolled a total of 1030 and 687 subjects receiving psyllium or placebo, respectively, were included in the meta-analysis. The studies were randomized placebo-controlled trials, double blinded or open label, on subjects with mild-to-moderate hypercholesterolemia. The dose of psyllium was between 3.0 and 20.4 g per day and intervention period was more than 2 weeks. Any type of diet background was permitted. Diet lead-in period was between 0 and 8 weeks. RESULTS: Compared with placebo, consumption of psyllium lowered serum total cholesterol by 0.375 mmol/l (95% CI: 0.257-0.494 mmol/l), and LDL cholesterol by 0.278 mmol/l (95% CI: 0.213-0.312 mmol/l). With random-effect meta-regression, a significant dose-response relationship were found between doses (3-20.4 g/day) and total cholesterol or LDL cholesterol changes. Regression model of total cholesterol was -0.0222+0.2061 x log (dose+1), and that of LDL cholesterol was 0.0485+0.1390 x log (dose+1). There was a time effect of psyllium on total cholesterol (equation: 6.3640-0.0316 x treatment period) and on LDL cholesterol (equation: 4.3134-0.0162 x treatment period), suggesting that psyllium reduced serum total cholesterol more quickly than LDL cholesterol. CONCLUSIONS: Psyllium could produce dose- and time-dependent serum cholesterol-lowering effect in mild and moderate hypercholesterolemic patients and would be useful as an adjunct to dietary therapy for the treatment of hypercholesterolemia.