European Journal of Clinical Nutrition (2009) 63, 821827

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ORIGINAL ARTICLE
Time- and dose-dependent effect of psyllium
on serum lipids in mild-to-moderate
hypercholesterolemia: a meta-analysis of
controlled clinical trials
Z-h Wei1, H Wang1, X-y Chen, B-s Wang, Z-x Rong, B-s Wang, B-h Su and H-z Chen

Department of Pharmacology and Biostatistics, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine,
Shanghai, China

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 doseresponse
relationship and its long-term lipid-lowering efficacy. This meta-analysis was primarily conducted to address the doseresponse
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: 0.2130.312 mmol/l). With random-effect meta-regression,
a significant doseresponse relationship were found between doses (320.4 g/day) and total cholesterol or LDL cholesterol
changes. Regression model of total cholesterol was
0.0222 0.2061  log (dose 1), and that of LDL cholesterol was
0.0485 0.1390  log (dose 1). There was a time effect of psyllium on total cholesterol (equation: 6.36400.0316 
treatment period) and on LDL cholesterol (equation: 4.31340.0162  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.
European Journal of Clinical Nutrition (2009) 63, 821827; doi:10.1038/ejcn.2008.49; published online 5 November 2008

Keywords: hypercholesterolemia; total cholesterol; LDL cholesterol; meta-analysis; randomized controlled trials

Introduction (Petchetti et al., 2007). It has been speculated that a

In recent years, there has been growing interest in the use of
dietary fibers in health maintenance and disease prevention
Correspondence: Professor H-z Chen, Department of Pharmacology and
Biostatistics, Institute of Medical Sciences, Shanghai Jiaotong University School
of Medicine, 200025, Shanghai, China.
E-mail: yaoli@shsmu.edu.cn
1 has been recommended as a safe and practical approach for
These authors contributed equally to this work.
Received 27 December 2007; revised 21 August 2008; accepted 18
September 2008; published online 5 November 2008
deficiency of soluble fibers in the Western diet might be
contributing to the epidemics of coronary heart disease
(CHD), diabetes mellitus and colonic cancer. Hypercholes-
terolemia has been identified as a prominent independent
risk factor in the development of CHD. Soluble fibers,
including those from psyllium husk, have been shown to
augment the cholesterol-lowering effects of a low-fat diet in
persons with hypercholesterolemia. Increasing dietary fiber
cholesterol reduction (NCEP ATPIII, 2001 and Brunner et al.,
2007).
 Time- and dose-dependent effect of psyllium on serum lipids
Z-h Wei et al
822
Psyllium is one of the highest sources of soluble mucilagi-
nous dietary fiber derived from seed husk of Plantago psyllium,
an annual plant grown in Mediterranean region, India, China
and other regions. It is mainly marketed in two forms, an
over-the-counter bulk-forming laxative under the trade name
Metamucil and psyllium-enriched health foods (Singh, 2007).
Psyllium is considered to be useful as an adjunct to dietary
therapy (step 1 or step 2 American Heart Association (AHA)
diet) in the treatment of patients with mild-to-moderate
hypercholesterolemia. The earliest clinical study (Garvin
et al., 1965) in a non-placebo-controlled pattern suggested
a significant cholesterol-lowering effect of psyllium
(Metamucil). Then the first double-blind, placebo-controlled
trial of psyllium was performed and it showed its effectiveness
in mild-to-moderate hypercholesterolemia (Anderson et al.,
1988). Subsequently, numerous clinical trials have investi-
gated the treatment effect of psyllium as an adjunct to
dietary modification. There was a universal feeling in all these
investigators that psyllium was a hypocholesterolemic agent.
However, most of these studies were poorly designed and only
enrolled a small number of patients; thus the results should
be considered inconclusive. In 1997, Olson et al. (1997)
conducted a meta-analysis involving 404 subjects with mild-
to-moderate hypercholesterolemia and found a beneficial
effect of psyllium-enriched cereal products on blood total
cholesterol and low-density lipoprotein (LDL) cholesterol.
Psyllium in a form other than cereal (for example, crackers,
bulk laxative) was not included in this study. More recently,
Brown et al. (1999) performed another meta-analysis to
quantify the cholesterol-lowering effect of major dietary fibers
including pectin, oat bran, guar gum and psyllium and found
that various soluble fibers reduced total and LDL cholesterol
by similar amounts, but the effect was small within the
practical range of intake. The latest meta-analysis, conducted
on individuals with mild-to-moderate hypercholesterolemia,
demonstrated that psyllium supplementation could signifi-
cantly lower serum total and LDL cholesterol concentrations
in subjects consuming a low-fat diet (Anderson et al., 2000a).
Despite the wealth of information that is available on the
association between the consumption of soluble dietary fiber
from psyllium and a cholesterol-lowering effect, the dose
response relationship and its long-term lipid-lowering
efficacy have not been defined. Thus it was of great interest
to conduct a meta-analysis with more updated evidence to
precisely determine the effect size of psyllium on decreasing
serum lipids and explore the doseresponse relationship and
long-term effects of psyllium on serum total cholesterol and
LDL cholesterol levels in individuals with mild-to-moderate
hypercholesterolemia.
Materials and methods
Identification of previous studies
A computerized literature search was conducted on the
MEDLINE, EMBASE, BIOSIS and PASCAL databases, using the
European Journal of Clinical Nutrition
terms psyllium or dietary fiber and blood lipids to identify
the clinical trials involving psyllium from 1966 to August
2005. In addition, FDA document, published reviews,
reference lists from clinical trials and conference abstracts
were also examined.
Trial selection
For inclusion in the meta-analysis, studies had to meet
the following criteria: (1) Trials were conducted on
human adults for the treatment of mild-to-moderate hyper-
cholesterolemia, not secondary to any recognized cause;
(2) they were controlled and had either a randomized
crossover or a parallel design; (3) they provided lipid
changes in the treatment and control groups to permit
the calculation of the treatment effect; (4) they had a
minimum intervention period of 2 weeks; (5) they had a low-
fat diet or controlled usual diet background. Disagreements
regarding criteria for admission to meta-analysis were
resolved by discussion and consensus. In all 22 of 39 studies
were selected for special review. Two studies (Stoy et al.,
1993; Spence et al., 1995), which met above criteria, were
excluded because they did not provide enough data to
compute the effect size and one (Wolever et al., 1994) was
excluded because subjects in the study were already
represented in another published study by the same group.
As two research reports (Sprecher et al., 1993; Jenkins et al.,
1997) involved two sub-groups, the data were treated as two
separate studies.
Data extraction
Data were extracted from the published reports by two
independent reviewers and disagreements resolved by dis-
cussion with the third reviewer. For each trial, the followings
were documented: country of origin, study population,
number and type of subjects, initial cholesterol concentra-
tion, type of psyllium preparation and used dose regimen,
nature of control group, background diet, method of
allocation, extent of blinding, study design (parallel or
crossover), treatment length, method of analysis, laboratory
method used to measure lipid levels, withdrawal and
so on.
Meta-analysis
The value of total cholesterol, LDL cholesterol, high density
lipoprotein (HDL) cholesterol and triglycerides were
presented in units of mmol/l. Results reported in mg/dl
were converted to mmol/l. For studies with parallel
group designs, lipid-lowering effect size was calculated
by subtracting the mean change in the control group from
that in the treatment group. The mean change was mean
baseline subtracted by mean end point value. For crossover
studies, the effect size was represented by the difference
of post-treatment lipid concentrations of the treatment
 Time- and dose-dependent effect of psyllium on serum lipids
Z-h Wei et al
823
Table 1 Characteristics of the studies included in the meta-analysis

Sources Country Study Diet lead-in Initial TC Background Type of Psyllium dose Duration
design period (d) concentration diet treatment (g/d) (d)
(mmol/l)

Anderson et al. (1988) US Parallel 14 4.788.28 Usual diet Metamucil 10.2 56

Bell et al. (1989) US Parallel 42 5.357.01 NCEP step 1 Metamucil 10.2 56
Bell et al. (1990) US Parallel 42 5.357.01 NCEP step 1 Cereal 3.0 42
Neal and Balm (1990) US Parallel 49 46.21 NCEP step 1 Metamucil 20.4 91
Levin et al. (1990) US Parallel 56 45.17 NCEP step 1 Metamucil 10.2 112
Anderson et al. (1991) US Parallel 56 5.177.76 NCEP step 1 Metamucil 10.2 56
Anderson et al. (1992) US Parallel 7 5.177.76 NCEP step 1 Cereal 12.0 42
Everson et al. (1992) US Crossover 46.2 Usual diet Metamucil 15.3 40
Sprecher et al. (1993) US Parallel 56 45.7 Low/high fat Metamucil 10.2 42
Summerbell et al. (1994) UK Parallel 21 5.27.8 Low fat Cereal 9.6 42
Wolever et al. (1994) Canada Crossover 28 46.21 NCEP step 2 Cereal 6.7 14
Roberts et al. (1994) Australia Crossover 28 6.007.75 Low fat Cereal 10.2 42
Maciejko et al. (1994) US Crossover 56 45.7 NCEP step 1 Metamucil 10.2 42
Jenkins et al. (1997) Canada Crossover 46.72 NCEP step 2 Cereal 9.4 30
Romero et al. (1998) Mexico Parallel 45.7 Usual diet Cookies 15.0 42
Davidson et al. (1998) US Parallel 56 LDL 3.365.68 NCEP step 1 Food 3.4/6.8/10.2 108
MacMahon and Carless (1998) UK Parallel 56 6.57.8 Low-fat Ispaghula husk 7.0/10.5 84
Anderson et al. (2000b) US Parallel 56 LDL 3.364.91 AHA step I Metamucil 10.2 182
Flannery and Raulerson (2000) US Parallel 45.7 Usual diet Food 6.0 112

Abbreviations: TC: total cholesterol; LDL: LDL cholesterol.

and control periods. A technique described by Anne (2002) Results

was used to pool the effect sizes from individual studies.
A positive value indicated a greater lipid reduction relative
to placebo.
Tests of heterogeneity were performed using Cochrane Q
test to determine whether they estimated for common
treatment effect. The significant level was a 0.2. But to
determine whether or not the Q statistic was significant, a
random-effect model was assumed.
Pooled effect size and its 95% confidence interval were
estimated by a fixed-effect or random-effect model. The
subgroup analyses were performed by dose (10.2 g/day),
psyllium-enriched foods, background diet (step I diet),
treatment period (8 weeks), design type (parallel design)
and clinical trial conducted in USA. Difference of lipid-
lowering effect between psyllium-enriched foods and bulk
laxative was tested by meta-regression (Berkey et al., 1995;
Houwelingen et al., 2002). The possibility of publication bias
was detected with funnel plot (Egger et al., 1997).
When more than one dose was studied, the mean lipid
change across all doses was used to provide an average effect
size. However, in the doseresponse analysis, each dose was
represented separately. Only clinical trials with parallel
group design were included in doseresponse analysis, as
the net change of lipid could only be estimated in this kind
of trials.
A random-effect meta-regression was performed to address
doseresponse relationships. The long-term effect of psy-
llium was explored by mixed-effect model for repeated
measure data.
All statistical analyses were performed using software
package SAS 9.13.
Description of trials
Study characteristics of all published trials included in the
meta-analysis were listed in Table 1. The studies were
undertaken in following five countries: United States, United
Kingdom, Canada, Australia and Mexico. They were either
parallel or crossover design. Subjects were mild-to-moderate
hypercholesterolemia (total cholesterol 44.78 mmol/l or
LDL cholesterol 43.36 mmol/l). Four studies had no dietary
lead-in period, whereas others had 28 weeks dietary lead-in
period. Most subjects consumed either a low-fat diet or an
NCEP step I or II diet during diet lead-in and therapy periods,
whereas those in four studies consumed controlled usual
diet. The therapy period ranged from 14 to 182 days. The
form was psyllium bulk laxatives or psyllium-enriched foods
with the dosage of 320.4 g/day. Data from 1717 persons
with hypercholesterolemia were included in this meta-
analysis.
Effects of psyllium on lipid
In the full dose range, psyllium significantly reduced
both serum total cholesterol and LDL cholesterol concen-
trations: 0.375 mmol/l (95% CI: 0.2570.494 mmol/l) and
0.278 mmol/l (95% CI: 0.2130.312 mmol/l) respectively,
among adults with mild-to-moderate hypercholesterolemia
(Table 2). The heterogeneity test of total cholesterol was
statistically significant, and that of LDL cholesterol was non-
significant. Psyllium also significantly reduced HDL choles-
terol, but by a much smaller amount: 0.0353 mmol/l (95%
CI: 0.00030.0514 mmol/l). Psyllium intake did not signifi-

European Journal of Clinical Nutrition

 Time- and dose-dependent effect of psyllium on serum lipids
Z-h Wei et al
824
Table 2 Pooled treatment effect of psyllium on serum lipid

Variables No. of studies No. of subjects Effect sizea (95% CI) (mmol/l) Heterogeneity (Q)

Total cholesterol 21 1717 0.375 (0.2570.494) 0.0001

LDL cholesterol 21 1696 0.278 (0.2130.312) 0.8825
HDL cholesterol 20 1430 0.0353 (0.00030.0514) 0.9980
Triglyceride 19 1397
0.0077 (
0.09070.0346) 0.9251
a
Effect size for each trial was computed as the difference of lipid level change between psyllium and placebo groups. The pooled effect size was calculated with
standard, fixed- or random-effect model. Any 95% CI that included zero indicated no significant result.

Anderson(1988) 0.730(0.119,1.341) n=26

Anderson(1988) 0.710(0.018,1.402) n=26
Bell(1989) 0.310(0.026,0.594) n=75
Bell(1989) 0.260(-0.051,0.571) n=75
Bell(1990) 0.220(-0.204,0.644) n=38
Bell(1990) 0.710(0.018,1.402) n=38
Neal(1990) 0.340(-0.161,0.841) n=54
Neal(1990) 0.440(-0.083,0.963) n=54
Levin(1990) 0.270(0.011,0.529) n=58
Levin(1990) 0.350(0.070,0.630) n=58
Anderson(1991) 0.390(0.047,0.733) n=52
Anderson(1991) 0.280(-0.080,0.640) n=52
Anderson(1992) 0.430(0.022,0.838) n=44
Anderson(1992) 0.550(0.126,0.974) n=44
Everson(1992) 0.260(-0.105,0.625) n=40
Everson(1992) 0.230(-0.223,0.684) n=40
Specher(1993)I 0.240(-0.042,0.522) n=81
Sprecher(1993)I 0.240(-0.077,0.557) n=81
Specher(1993)II 0.350(-0.007,0.707) n=37
Sprecher(1993)II 0.470(0.057,0.883) n=37
Summerbell(1993) 0.190(-0.215,0.595) n=37
Summerbell(1994) 0.280(-0.179,0.739) n=37
Roberts(1994) 0.20(0.011,0.389) n=158
Roberts(1994) 0.210(0.011,0.409) n=162
Wolever(1994) 0.370(0.051,0.689) n=84
Wolever(1994) 0.430(0.097,0.763) n=84
Maciejko(1994) 0.240(-0.476,0.956) n=36
Maciejko(1994) 0.190(-0.589,0.969) n=36
Jenkins(1997)I 0.230(-0.089,0.549) n=64
Jenkins(1997)I 0.270(-0.090,0.630) n=64
Jenkins(1997)II 0.210(-0.275,0.695) n=54
Jenkins(1997)II 0.250(-0.235,0.735) n=54
Romero(1998) 1.060(0.495,1.625) n=20
Romero(1998) 0.980(0.438,1.522) n=20
MacMahon(1998) 0.240(0.05,0.430) n=266
MacMahon(1998) 0.215(-0.024,0.454) n=283
Davidson(1998) 0.220(-0.015,0.455) n=196
Davidson(1998) 0.143(-0.122,0.408) n=196
Anderson(2000) 0.270(0.105,0.43) n=248
Anderson(2000) 0.990(0.788,1.192) n=248
Flannery(2000) 0.130(-0.375,0.635) n=28
Flannery(2000) 0.160(-0.383,0.703) n=28
-1.0 -0.5 0 0.5 1.0 1.5 2.0
-1 -0.5 0 0.5 1.0 1.5 2.0
Figure 2 The effect size (and 95% CI) of psyllium on LDL
Figure 1 The effect size (and 95% CI) of psyllium on total cholesterol of all studies included in the meta-analysis. The
cholesterol of all studies included in the meta-analysis. The horizontal lines denoted the 95% CIs.
horizontal lines denoted the 95% CIs.

cantly affect serum triacylglycerol concentrations. Figures 1
and 2 showed the net effect of consumption of psyllium on
total cholesterol and LDL cholesterol levels for each study
included in the meta-analysis. To explore heterogeneity,
funnel plots for total cholesterol and LDL cholesterol were
drawn and shown in Figure 3. Egger test displayed that
asymmetry
0.3999 (P 0.7058) for total cholesterol,
suggesting that publication bias was not confirmed, but the
phenomenon of large effect and small sample could be
concluded. The asymmetry of LDL cholesterol was 0.9424
(P 0.0399), indicating that both publication bias and the
phenomenon of large effect and small sample existed
simultaneously.
Doseresponse relation of psyllium
There was a significant doseresponse relationship between
doses (320.4 g/day) and changes of serum total cholesterol
or LDL cholesterol levels. The regression between log term of
dose and measurement was estimated with random-effect
regression model. The regression model of total cholesterol
was
0.0222 0.2061  log (dose 1), and that of LDL
cholesterol was 0.0485 0.1390  log (dose 1). Although
the two models were both statistically significant (both the
P-values were smaller than 0.0001), the regression coefficients
were relatively small and the independent variable was
log-transformed. Thus greatly increasing dosages of psyllium
might not correspondingly produce a clinically significant
difference in the lipid-lowering effect across a dose range of
320.4 g/day. On the other hand, we fitted a weighted linear
model to explore the relationship between the percent
reduction of LDL cholesterol (calculated as baseline

end point=baseline100%) and dose of psyllium (Figure 4).
Results showed that there was a moderate correlation,
and the regression equation was: 2.200 0.685  dose
(P 0.0454). According to this equation, consumption of

European Journal of Clinical Nutrition

 Time- and dose-dependent effect of psyllium on serum lipids
Z-h Wei et al
825
12 7.5

Total cholesterol level (mmol/L)

10
7.0
Precision (1/SE)

Anderson(2000)
8

6 6.5
Placebo
4 Romero(1998)
6.0
2 Anderson(1988)
5.5 Psyllium
0
0.2 0.4 0.6 0.8 1.0 1.2
Effect size (mmol/L) 5.0
0 5 10 15 20 25 3
14 Treatment (week)

12 5.2

LDL cholesterol level (mmol/L)

Precision (1/SE)

10
4.8
8
6 4.4
Romero(1998) Placebo
4
Anderson(1988) 4.0
2
Psyllium
0
0.2 0.4 0.6 0.8 1.0 1.2 3.6
Effect size (mmol/L)
3.2
Figure 3 Funnel plot of all trials in the meta-analysis on total 0 5 10 15 20 25 30
cholesterol-lowering (upper) and LDL cholesterol-lowering (lower) Treatment (week)
effects of psyllium.
Figure 5 The time-effect relation of psyllium on serum total
cholesterol (upper) and LDL cholesterol (lower) levels. m: placebo,
K: psyllium. The line was estimated by random-effect model
Percent Reduction in LDL-C (%)

30 for repeated measurements. The time effect was fixed in the

model.
25

20
15
10
5 cholesterol was 6.36400.0316  treatment period, and that
0
0 3 6 9
Dose (g/day)
Figure 4 Relation between the percent reduction in LDL cholesterol
(LDL-C) and dose of psyllium. The percent change of LDL cholesterol
was calculated as baseline
end point=baseline100%: The line
was estimated by weighted linear model. Plot showed a positive and
moderate association between dose of psyllium and percent
decrease in LDL cholesterol.
psyllium 5, 10 and 15 g/day could result in 5.6, 9.0 and
12.5% decrease of LDL cholesterol level respectively.
Long-term effects of psyllium on lipid
There was a long-term effect of psyllium on total cholesterol
and LDL cholesterol (Figure 5). The equation was fitted using
a mixed-effect model for a repeated measurement. Through-
out the treatment period, serum total cholesterol and LDL
cholesterol levels of psyllium group reduced faster than that
of the placebo group (Po0.0001). The equation of total
of LDL cholesterol was 4.31340.0162  treatment period,
12 15 18 21 suggesting that, along with time, total cholesterol reduced
more quickly than LDL cholesterol.
Type of intervention
Psyllium, as either bulk laxatives or enriched foods, could
significantly reduce serum total cholesterol and LDL choles-
terol levels. The effect sizes of psyllium as bulk laxatives on
total cholesterol and LDL cholesterol were 0.442 mmol/l
(95% CI: 0.2100.674 mmol/l) and 0.300 mmol/l (95%
CI: 0.1670.430 mmol/l) respectively, whereas that of
psyllium as enriched foods were 0.320 mmol/l (95%
CI: 0.1620.477 mmol/l) and 0.260 mmol/l (95% CI:
0.1800.340 mmol/l), respectively. The form of psyllium
seemed to have no significant influence on lipid-lowering
effects (P 0.2367 for total cholesterol and P 0.5688 for
LDL cholesterol).

European Journal of Clinical Nutrition

 Time- and dose-dependent effect of psyllium on serum lipids
Z-h Wei et al
826
Table 3 Pooled treatment effect on total and LDL cholesterol in subgroups of trials defined by study design features
Subgroup No. of trials
Dose 10.2 g/day 10
Psyllium-enriched foods 11
Step I diet 9 0.420
Duration 8 weeks 8 0.357
Parallel design 15
Study in USA 14
a
Effect size for each subgroup of total cholesterol was computed by random-effect model and that of LDL cholesterol by fixed-effect model. TC: total cholesterol;
LDL: LDL cholesterol.
Subgroup analysis
Effect size of each subgroup was similar to the pooled effect
size of all studies in this meta-analysis (Table 3).
Discussion
In this meta-analysis of 21 studies, subjects who admini-
strated psyllium bulk laxatives or enriched foods had
significantly decreased total cholesterol, LDL cholesterol
and HDL cholesterol concentrations. Compared with place-
bo control, the mean decrease of total cholesterol, LDL
cholesterol and HDL cholesterol were 0.375, 0.278 and
0.0353 mmol/l, respectively. But for triglycerides, there was
little effect.
We established a doseresponse relationship between
psyllium and serum total and LDL cholesterol levels.
However, it was a logarithmic relationship, which indicated
that greatly increasing dosage of psyllium did not produce a
correspondingly large effect size. Although psyllium was well
tolerated, high dosage (20.4 g per day) might cause diarrhea
(Neal and Balm, 1990).
Long-term intake of psyllium could cause sustained
decrease in the total and LDL cholesterol levels. It had been
estimated that a fall of 0.6 mmol/l in total cholesterol would
reduce subsequent cardiovascular risk by 50% among those
aged 40 and by 20% among those aged 70 (Betteridge, 1994).
Every 1% reduction in LDL cholesterol could reduce the risk
of CHD by 1.22.0% (Katan et al., 2003). Based on the result of
this meta-analysis, after consuming psyllium for 20 weeks,
serum total cholesterol level could be reduced from baseline
level (about 6.36 mmol/l) to 5.73 mmol/l and LDL cholesterol
concentration could be dropped from 4.31 to 4.0 mmol/l with
the decrease rate as 9%. And after psyllium consumption for
about 1 year and a half, the LDL cholesterol could get to
3.1 mmol/l (the upper limit of the reference range).
CHD is a major cause of death in United States and most
Western countries. Blood cholesterol is a major risk factor of
coronary heart disease. Dietary and pharmacological reduc-
tions in total and LDL cholesterol decrease the risk of
coronary events, so dietary has been recommended as a safe
and practical approach for cholesterol reduction. Psyllium is
European Journal of Clinical Nutrition
Effect sizea (95% CI) mmol/l
TC LDL
0.388 (0.193,0.583) 0.267 (0.185, 0.309)
0.320 (0.162, 0.477) 0.260 (0.180, 0.340)
(0.211, 0.629) 0.271 (0.175, 0.320)
(0.203, 0.512) 0.283 (0.164, 0.343)
0.415 (0.264, 0.567) 0.292 (0.215, 0.331)
0.396 (0.238, 0.554) 0.287 (0.203, 0.329)
one of the most effective lipid-lowering agents. In 1998, FDA
ruled that labels on certain foods containing soluble fiber from
psyllium seed husk, such as certain breakfast cereals, might
claim that these foods, as part of a diet low in saturated fat and
cholesterol, may reduce the risk of coronary heart disease.
Newer dietary approaches combining cholesterol-lowering
drugs or foods may offer another option. The synthesized
effects of a combination therapy including psyllium and low-
dose statins (Moreyra et al., 2005) or plant sterols (Shrestha
et al., 2006) have been demonstrated in clinical trials.
We believed that the results of this meta-analysis repre-
sented a conservative estimate of psyllium effect on lipid-
lowering. We could conclude that there was a publication
bias in this meta-analysis, based on the results of funnel
plots. The publication bias was mainly caused by large effect
but small trial phenomenon. The effect size would be larger
if all those small trials were published and selected into the
meta-analysis.
Consuming psyllium as a bulk-forming fiber laxative is
functionally equivalent to consuming psyllium-enriched foods.
Clinical studies evaluating psyllium administered as bulk
laxatives were conducted in a fashion similar to the studies
conducted with psyllium-enriched foods, including patient
selection criteria and regimen, thus efficacy should be compar-
able for bulk laxative and enriched foods studies. The results of
this meta-analysis confirmed that the effect of these two forms
on serum lipid levels has a non-significant difference. Having
both available options would provide alternatives to improve
the compliance of a fiber intake recommendation. Moreover,
psyllium is one of the most commonly used over-the-counter
drug for the treatment of chronic constipation, especially in the
elders who have a high incidence of hypercholesterolemia,
thus psyllium would provide another potential benefit for
them due to its efficacy in lowering serum cholesterol levels at
the dose in common use.
Acknowledgements
This work was partially supported by Cooperative Program
of Rhone-Alps Region and Shanghai. We thank Professor
Jean-Pierre Boissel and Dr Michael Cucherat (Institute of

Clinical Pharmacology, Lyon University I, France) for
expert advice.
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