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ORIGINAL COMMUNICATION
Therapeutic effects of psyllium in type 2 diabetic
patients
M Sierra
1
*, JJ Garcı
´
a
1
, N Ferna
´
ndez
1
, MJ Diez
1
, AP Calle
1
and Farmafibra Group
{
1
Department of Pharmacology, Toxicology and Nursing, University of Leo
´
n, Leo
´
n, Spain
Objective: The aim of this study was to evaluate the effects of psyllium in type 2 diabetic patients.
Design: The study included three phases: phase 1 (1 week), phase 2 (treatment, 14 g fibre=day, 6 weeks) and phase 3 (4 weeks).
At the end of each phase a clinical evaluation was performed after the ingestion of a test breakfast of 1824.2 kJ (436 kcal).
Measurements included concentrations of blood glucose, insulin, fructosamine, GHbA
1c
, C-peptide and 24 h urinary glucose
excretion. In addition, uric acid, cholesterol and several mineral and vitamin concentrations were also evaluated.
Setting: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of Leo
´
n
(Spain).
Subjects: Twenty type 2 diabetic patients (12 men and 8 women) participated in the study with a mean age of 67.4 y for men
and 66 y for women. The mean body mass index of men was 28.2 kg=m
2
and that of women 25.9 kg=m
2
.
Results: Glucose absorption decreased significantly in the presence of psyllium (12.2%); this reduction is not associated with an
important change in insulin levels (5%). GHbA
1c
, C-peptide and 24 h urinary glucose excretion decreased (3.8, 14.9 and 22.5%,
respectively) during the treatment with fibre (no significant differences) as well as fructosamine (10.9%, significant differences).
Psyllium also reduced total and LDL cholesterol (7.7 and 9.2%, respectively, significant differences), and uric acid (10%,
significant difference). Minerals and vitamins did not show important changes, except sodium that increased significantly after
psyllium administration.
Conclusions: The results obtained indicate a beneficial therapeutic effect of psyllium (Plantaben
1
) in the metabolic control of
type 2 diabetics as well as in lowering the risk of coronary heart disease. We also conclude that consumption of this fibre does
not adversely affect either mineral or vitamin A and E concentrations. Finally, for a greater effectiveness, psyllium treatment
should be individually evaluated.
European Journal of Clinical Nutrition
(2002) 56, 830 – 842. doi:10.1038=sj.ejcn.1601398
Keywords: type 2 diabetic patients; ispaghula husk; psyllium; dietary fibre; glucose; insulin; cholesterol; capillary blood glucose;
metabolic variables
Introduction
Dietary fibre has significant gastrointestinal effects and it is a
mainstay of treatment for constipation and haemorrhoids.
Insoluble fibre is most effective for the treatment of these
pathologies and an increased intake of soluble dietary fibre
appears to benefit patients with diabetes mellitus (Gray,
1995).
The advantages of high-fibre diets for diabetic patients
have been said to include lowering of serum lipids, assisted
weight reduction and maintenance, and lowering of blood
glucose levels (Kiehm et al, 1976; Anderson 1985a, b).
It is especially the gel-forming, water-soluble dietary
fibre components such as guar gum, pectin and psyllium
that have beneficial effects on carbohydrate metabolism
(Jenkins et al, 1977; Chuang et al, 1992; Ellis et al, 1991;
Fairchild et al, 1996; Gatenby et al, 1996; Wursch &
Pi-Sunyer, 1997).
*Correspondence: M Sierra, Department of Pharmacology, Toxicology
and Nursing, University of Leo
´
n, Leo
´
n, Spain.
E-mail: dftmsv@unileon.es
Guarantors: Matilde Sierra and Juan J Garcı
´
a.
Contributors: MS was mainly responsible for all stages of the study,
including the study design, discussion and interpretation of results
and writing of the paper. JJG participated in the discussion and
interpretation of results and in the statistical analysis. NF and MJD
were involved in the literature searches and data collection and entry
and assisted with the preparation of the paper. APC carried out the
analytical determinations and diet control. The Farmafibra Group was
in charge of the medical management of subjects and sample
collection and preparation.
{
The Farmafibra Group is: Juan C A
´
lvarez, Demetrio Carriedo, Luis J
Castro, Mariano de la Torre, Ara
´
nzazu Gonza
´
lez, M Angeles Gonza
´
lez,
Vicente Mora
´
n, Carlos Prieto and Ana M Sahagu
´
n.
Received 20 June 2001; revised 24 October 2001;
accepted 3 December 2001
European Journal of Clinical Nutrition (2002) 56, 830–842
ß 2002 Nature Publishing Group All rights reserved 0954–3007/02 $25.00
www.nature.com/ejcn
Psyllium or ispaghula husk (the husk of the seeds of
Plantago ovata) is a mixture of neutral and acid polysacchar-
ides with a rest of galacturonic acid. The polysaccharides are
built up from the monomers
D-xylose and L-arabinose, and
ispaghula husk contains 67% pentosanes. Ispaghula husk is a
gel-forming (water-soluble) fibre which has been used in
treatment for constipation for many years. During the last
two decades, several studies have been carried out to inves-
tigate whether ispaghula interferes with normal intestinal
absorption of carbohydrate in healthy volunteers (Jarjis et al,
1984; Sierra et al, 2001) and in type 1 (Florholmen et al,
1982; Uribe et al, 1985) and type 2 diabetic patients (Sartor
et al, 1981; Jarjis et al, 1984; Pastors et al, 1991). The effect
of psyllium on fasting plasma cholesterol in hypercholester-
olaemic patients has also been evaluated (Bell et al, 1989)
and in obese and diabetic patients (Frati-Munari et al, 1983).
The results obtained in these studies indicate that, in gen-
eral, ispaghula administration yields to a decrease in glycae-
mia, insulinaemia and cholesterolaemia, but Jarjis et al,
(1984) failed to detect significant glucose blunting.
In the present study we have evaluated the therapeutic
effect of psyllium on glycaemic control in type 2 diabetic
patients treated with glibenclamide and under dietary reg-
ulations. The effect on the total serum cholesterol concen-
trations and the distribution of serum cholesterol between
the high-density-lipoprotein (HDL) and the low-density-
lipoprotein (LDL) was also established. In addition, several
hepatic, renal and haematological parameters were evalu-
ated.
Subjects and methods
Patients
Twenty type 2 diabetic patients (12 men and 8 women)
participated in the study. The mean age of the men was
67.4 y (range 50 – 80 y) and that of the women 66 y (range
54 – 79 y). The mean body mass index (BMI) of men was
28.2 kg=m
2
(range 25 – 29.6 kg=m
2
) and of women 25.9 kg=m
2
(range 20 – 29.8 kg=m
2
).
The duration of diabetes in all the volunteers eligible for
the study was between 2 and 30 y (mean 10.4 y) in men and
between 2 and 18 y (mean 7 y) in women. Diabetes was
treated in all patients with a sulphonylurea (glibenclamide)
and by conventional dietary restrictions. The diet followed
by the volunteers was the same for all of them during the
study. This diet is recommended to diabetic patients by the
Program of INSALUD (National Institute of Health) and
contains 55% of carbohydrate, 30% of fat (10% of saturated
fat), 15% of protein and 25 g of fibre per day.
All subjects were questioned to assess subjective gastro-
intestinal side effects of the fibre, if any, but not one of the
patients communicated any adverse effect. Each subject had
normal stool consistence and frequency. Four patients who
suffered from constipation showed a clear improvement
during the treatment with fibre. All the volunteers success-
fully completed the study.
Study design
The study was conducted on an outpatient basis. The volun-
teers had no history of gastrointestinal disease and other
major illnesses, and each subject served as his own control.
The protocol was approved by the Human Ethical Commit-
tee of the University and INSALUD of Le
´
on, Spain, and
performed in accordance with the principles of the Declara-
tion of Helsinki. Written informed consent was obtained
from each subject.
Patients were admitted to an open study for its entire
duration. The study protocol included three different phases
(phase 1, phase 2 (treatment) and phase 3) and at the end of
each phase, the therapeutic and dietary accomplishment
were evaluated by the patient and one of the investigators.
The study began with a 1 week period (phase 1) over
which subjects followed a diet for diabetes and received the
sulphonylurea. This was followed by the phase 2 (treatment
phase, 6 weeks) over which patients continued with the diet
and the sulphonylurea, and also received 3.5 g of psyllium
(one dose of Plantaben
1
, orange flavoured, sugar-free,
Madaus, S.A., Spain) four times a day: before breakfast,
lunch, afternoon snack and dinner (14 g of psyllium=day).
Subjects were instructed to mix each fibre packet in 250 ml of
water, followed by 50 ml water for glass cleaning, and to
drink the mixture before each meal. Phase 3 (4 weeks) was
carried out after a 2-week washout interval. As in the phase 1,
subjects followed the diet and received sulphonylurea.
During phases 1 and 3, the patients received the same
volume of water (300 ml) as in phase 2 without psyllium
before meals in order to avoid changes in gastric emptying.
A clinical examination was performed at the end of each
phase. On each occasion, and after overnight fast, they
ingested a standard breakfast (Ebeling et al, 1988) of
1824.2 kJ (436 kcal; 53% carbohydrate, 26% protein and
21% fat), which consisted of 80 g low-fat boiled ham, two
slices (60 g) of white bread and 200 ml low-fat milk with non-
sweetened black coffee. Before breakfast, one dose of the
fibre was given.
Blood samples (7 ml) were drawn through a butterfly
cannula placed in the forearm at 7 15, 0, 10, 20, 30, 45,
60, 75, 90 and 120 min after breakfast ingestion for blood
glucose estimation, and at 7 15, 0, 30, 60, 90 and 120 min
blood insulin concentrations were also determined. The
values calculated at 7 15 and 0 min were averaged to
obtain glucose and insulin fasting values.
Blood samples obtained at time 0 were also used to
determine several biochemical parameters (uric acid, total,
HDL and LDL cholesterol) as well as different minerals
(calcium, phosphorous, sodium, potassium, magnesium,
iron) and vitamins (A and E) whose blood levels can be
modified by the presence of fibre. In addition, other para-
meters related to patient status were also determined: glyco-
sylated haemoglobin (GHbA
1c
), fructosamine and C-peptide
in serum as well as 24 h urinary glucose and C-peptide
excretion. The urine was collected from ingesting the test
breakfast until next morning.
Therapeutic effects of psyllium
M Sierra
et al
831
European Journal of Clinical Nutrition
Methods
Serum glucose was measured with the Schmidt method
(Schmidt, 1961) using an autoanalyser (Hitachi, mod. 704,
Tokyo, Japan). Insulin concentrations were determined with
an immunoradiometric assay (IRMA assay kit, Biosource
Europe, S.A., Nivelles, Belgium). Serum vitamin A and E
were determined by high-pressure liquid chromatography
(HPLC; Driskell et al, 1982). An enzymatic colorimetric
method was used for the determination of cholesterol (Boeh-
ringer-Mannheim, GmbH, Mannheim, Germany). The HDL
fraction was analysed after precipitation with magnesium
chloride and dextrane sulphate (Finley et al, 1978). LDL
cholesterol was calculated by the formula of Friedewald
et al (1972). GHbA
1c
was determined by commercial ion-
exchange chromatography (Quick-Step Fast Hemoglobin
System
1
, Isolab Inc., Akron, OH, USA). Minerals and uric
acid were determined by using an autoanalyser Hitachi,
model 704 (Tokyo, Japan). Serum fructosamine was analysed
in triplicate using the Cobas Fara II (Lloyd & Marples, 1984).
Urinary glucose concentrations were evaluated by using an
enzymatic method (Weatherburn & Logan, 1966). Finally, C-
peptide was determined by RIA (Kuzuya et al, 1976).
During the study, except the 2 week washout interval,
patients measured their diurnal blood glucose profile at
home twice a week (on Tuesday and on Thursday). On
these days six measurements were done (before and 90 min
after breakfast, lunch and dinner) using Glucostix
1
(Miles
Limited, Glamorgan, UK) test strips that were read with a
Glucometer (Miles Laboratories Inc., Elkhart, IN, USA). The
number of blood glucose determinations per patient was
132, during the three periods (12 in phase 1, 72 in phase 2,
48 in phase 3).
Statistical analysis
Arithmetic means and s.d.s were calculated from the results
measured. The data obtained from the three phases were
compared for statistical significance by Friedman’s test, at
P < 0.05 and, when the results were significant, Wilcoxon
pairwise comparisons with Bonferroni correction were used,
except for capillary glycaemia, where Kruskal – Wallis test
and Mann – Whitney U-test were employed. All analyses
were performed by using the Statgraphics Plus for Windows
2.0 (Manugistic Inc., Rockville, MA, USA).
Results
Serum glucose
The extent of glucose absorption decreased in the presence
of psyllium when mean values were considered (Table 1 and
Figure 1). Differences in mean concentrations at different
sampling times were significant, except when the values
obtained at time 0 for phases 2 and 3 were compared.
Significant differences were also established for mean con-
centrations among subjects. C
max
decreased nearly 10% in
Table 1 Serum glucose concentrations (mmol=l) in 20 type 2 diabetic patients after a test breakfast
Phase 1 Phase 2 Phase 3
Time (min) x
¯
s.d. CV (%) x
¯
s.d. CV (%) x
¯
s.d. CV (%)
0
b
8.66 2.22
c
25.7 7.73 1.98 25.6 8.21 2.32 28.2
10
a,b
9.43 2.29
c
24.3 7.98 1.96 24.6 8.85 2.45
c
27.7
20
a,b
10.81 2.45
c
22.7 9.05 2.01 22.2 10.29 2.61
c
25.4
30
a,b
12.02 2.82
c
23.5 10.46 2.15 20.6 11.93 2.59
c
21.7
45
a,b
13.52 2.92
c
21.6 12.06 2.21 18.4 13.29 2.49
c
18.7
60
a,b
14.00 2.67
c
19.1 12.83 2.58 20.2 14.27 2.93
c
20.5
75
a,b
14.19 3.02
c
21.3 12.51 2.81 22.5 14.04 3.23
c
23.0
90
a,b
13.63 3.12
c
22.9 11.93 3.12 26.2 13.52 3.63
c
26.8
120
a,b
12.54 3.53
c
28.1 10.76 3.43 31.9 11.91 3.63
c
30.5
a
Significant differences among phases (Friedman’s test,
P
< 0.05).
b
Significant differences among subjects (Friedman’s test,
P
< 0.05).
c
Significant differences with phase 2 (Wilcoxon modified test, for conditions see text).
Figure 1 Mean serum glucose concentrations in 20 type 2 diabetic
patients after test breakfast.
Therapeutic effects of psyllium
M Sierra
et al
832
European Journal of Clinical Nutrition
the phase 2 (treatment) curve when compared with the
values obtained in the phases 1 and 3. The rate of glucose
absorption was similar during phases 2 and 3 (t
max
¼ 60 min)
and less than in phase 1 (t
max
¼ 75 min).
The area under the serum glucose concentration – time
curve (AUC) was 12.2% lower in the presence of fibre than
that obtained at the end of phase 1 and 11.9% lower than
that obtained at the end of the phase 3 (significant differ-
ences, Wilcoxon’s test).
When accumulated areas (AUC
t
, where t is the time over
which AUC has been calculated) were considered, significant
differences were also found between phases 1 and 3 data
when compared with those obtained in the phase 2, except
at 10 min between phases 2 and 3 (Wilcoxon’s test).
Figure 2 (a) Individual serum glucose-time curves in 10 type 2 diabetic patients after test breakfast.
Therapeutic effects of psyllium
M Sierra
et al
833
European Journal of Clinical Nutrition
Large interindividual variations were observed in glu-
cose concentrations, with CV ranging from 18.7 to
31.9% (Table 1) and, because of this, it is important to
evaluate individual curves (Figure 2a and b) in addition
to mean curves (Figure 1). Thus, in 10 patients (numbers
1 – 10,Figure2a),glucoseconcentrationsandAUC
values were clearly lower at the end of the phase 2
than at the end of phases 1 and 3, with AUC decreases
Figure 2 (b) Individual serum glucose-time curves in 10 type 2 diabetic patients after test breakfast.
Therapeutic effects of psyllium
M Sierra
et al
834
European Journal of Clinical Nutrition
up to 34%. Five volunteers (numbers 11 – 15) showed
higher values during the phase 1 than during phases 2
and 3, and in three of them (numbers 11 – 13), the
curves obtained in phases 2 and 3 were very similar.
Finally, in five subjects (numbers 16 – 20) the three
curves were very similar.
Serum insulin
AUC decreased a 5% in phase 2 in comparison with the value
obtained in phase 1, and it was 15% lower than in phase 3
(no significant differences, Friedman’s test, at P < 0.05).
Mean curve shapes (Figure 3) were similar in the three
phases.
The value of C
max
(Table 2) was lower in the presence of
fibre (348.6 pmol=l) than in phases 1 (369.0 pmol=l) and 3
(394.8 pmol=l), but these differences were not significant.
The individual insulinaemic responses were very differ-
ent, with CVs for the mean concentrations higher than those
obtained for glucose. In our opinion, this fact reflects the
different states of type 2 diabetes evolution in which patients
can be. When phases 1 and 3 are compared, some patients
show a high decrease in AUC mean values (up to 47.6%),
while in others this value is scarcely modified or even
increases (up to 45% in one patient).
Examining the corresponding curves it can be observed
that nine patients showed low insulin concentration values.
Five of them had high glucose levels (numbers 3, 4, 10, 11
and 16), reaching concentrations over 16.7 mmol=l; in four
patients (numbers 9, 13, 14 and 20), the glucose concentra-
tions were high, with values greater than 13.3 mmol=l; in the
other volunteer (number 18), the glucose concentrations at
the end of the curve were over the basal levels. Five volun-
teers (numbers 1, 5, 7, 8 and 19) show high insulin concen-
Figure 3 Mean serum insulin concentrations in 20 type 2 diabetic patients after test breakfast.
Table 2 Serum insulin concentrations (pmol=l) in 20 type 2 diabetic patients after a test breakfast
Phase 1 Phase 2 Phase 3
Time (min) x
¯
s.d. CV (%) x
¯
s.d. CV (%) x
¯
s.d. CV (%)
0
a
85.6 46.3 54.0 85.1 50.4 59.3 97.2 40.0 41.1
30
a
211.7 126.6 59.8 186.5 90.9 48.8 201.8 110.2 54.6
60
a
332.3 225.7 67.9 327.0 199.3 61.0 386.3 255.1 66.0
90
a
369.1 277.4 75.2 348.7 217.0 62.2 395.0 289.6 73.3
120
a
257.0 203.3 79.1 250.8 187.6 74.8 304.4 225.1 73.9
Friedman’stest(
P
< 0.05).
a
Significant differences among subjects. No significant differences among phases were found.
Therapeutic effects of psyllium
M Sierra
et al
835
European Journal of Clinical Nutrition
trations during the administration of psyllium, and these
values were generally higher than in phase 1 and lower than
in phase 3. The three curves were similar in three patients
(numbers 2, 6 and 15), except in the last times in two of
them (numbers 2 and 6). Finally, in two subjects (numbers 12
and 17), the insulin concentrations decreased in the pre-
sence of fibre, when compared with those obtained in phase
1, and were similar to the values shown in the phase 3 curve.
Capillary glycaemia
A total of 120, 678 and 441 values of postprandial glucose
concentrations were obtained, corresponding respectively to
phases 1, 2 (treatment) and 3 of the study. The same number
of preprandial data were evaluated. In general, there was a
good compliance, but one patient only measured the glucose
concentrations during phase 1; another patient forgot 2 days
during phase 2 and, finally, one patient failed one day during
phase 3.
Taking into account the mean values (Table 3), fasting
blood glucose was slightly lower (4.5%) during phases 2 and
3 than during phase 1 (no significant differences, Kruskall –
Wallis test, at P < 0.05). The mean preprandial values
corresponding to lunch and dinner were also slightly lower
and differences were not significant (Kruskall – Wallis test, at
P < 0.05).
Mean postprandial glucose levels decreased during phase
2: 10.2% vs phase 1 and 5.3% vs phase 3 (significant differ-
ences, Mann – Whitney U-test).
The mean postprandial glucose concentrations corre-
sponding to breakfast, lunch and dinner were always lower
during phase 2 than during phases 1 and 3. The decreases in
these values were 13.8% in breakfast, 7.8% in lunch and
8.2% in dinner (phase 2 vs phase 1), and 4.0% in breakfast,
6.7% in lunch and 4.4% in dinner (phase 2 vs phase 3).
Significant differences were found between postprandial
capillary glycaemia obtained after breakfast between phases
1 and 2. Important interindividual variations were also
found in this parameter. In this way, some patients show
decreases for postprandial glycaemia close to 30%, while in
two subjects this parameter is scarcely modified.
Other parameters related to diabetes
Table 4 summarises several parameters related to diabetes.
The treatment with fibre reduced slightly glycosylated hae-
moglobin (GHbA
1c
; 3.8% vs phase 1 and 5.5% vs phase 3),
although no significant differences were observed. Similar
results were obtained with fructosamine (fell by 10.9% on
fibre vs phase 1 and by 7.8% vs phase 3) and with blood C-
peptide (fell by 14.9% on fibre vs phase 1 and by 10% vs
phase 3). The statistical evaluation showed significant differ-
ences for fructosamine when we compared the value
Table 3 Capillary glycaemia (mmol=l) in 20 type 2 diabetic patients before and 90 min after meals
Phase 1 Phase 2 Phase 3
Time (min) x
¯
s.d. CV (%) x
¯
s.d. CV (%) x
¯
s.d. CV (%)
Before breakfast
b
7.72 1.90 24.61 7.34 1.88 25.59 7.46 1.88 25.16
After breakfast
a,b
11.58 3.31
c
28.59 9.98 2.81 28.16 10.39 3.13 30.14
Before lunch
b
7.27 2.64 36.24 6.69 2.49 37.20 6.68 2.33 34.86
After lunch
b
9.67 4.14 42.77 8.92 2.76 30.91 9.56 3.11 32.58
Before dinner
b
6.73 2.79 41.40 6.47 2.56 39.49 6.43 2.27 35.38
After dinner
b
10.02 3.28 32.74 9.20 2.60 28.21 9.63 2.83 29.35
a
Significant differences among phases (Kruskall – Wallis’s test,
P
< 0.05).
b
Significant differences among subjects (Kruskall – Wallis’s test,
P
< 0.05).
c
Significant differences with phase 2 (Mann – Whitney
U
-test, for conditions see text).
Table 4 Mean values ( s.d.) of different parameters related to diabetes measured in 20 type 2 diabetic patients
after a test breakfast
Phase 1 Phase 2 Phase 3
x
¯
s.d. CV (%) x
¯
s.d. CV (%) x
¯
s.d. CV (%)
Fructosamine (mmol=l)
a,b
3.0 0.9
c
29.6 2.7 0.7 25.3 2.9 0.7
c
22.4
Blood C-peptide (nmol=l)
b
0.91 0.44 48.6 0.78 0.34 43.8 0.86 0.40 45.9
Glycosylated HbA
1c
(%)
b
6.8 1.0 14.2 6.5 0.9 13.6 6.9 1.2 17.0
Urinary 24 h glucose excretion (mmol)
a,b
20.7 24.4 117.8 14.3 20.8 145.4 16.3 23.0
c
140.8
a
Significant differences among phases (Friedman’s test,
P
< 0.05).
b
Significant differences among subjects (Friedman’s test,
P
< 0.05).
c
Significant differences with phase 2 (Wilcoxon modified test, for conditions see text).
Therapeutic effects of psyllium
M Sierra
et al
836
European Journal of Clinical Nutrition
obtained in phase 2 with those recorded in phases 1 and 3. In
these parameters important interindividual variations were
observed.
Twenty-four hour urinary glucose excretion was 22.5%
lower at the end of the treatment than in phase 1 and 14.6%
than in phase 3, however, significant differences (Wilcoxon’s
test) were only found between the phases 2 and 3. In this
case, interindividual variations were even greater.
Other parameters
Serum total cholesterol concentrations decreased significantly
under psyllium treatment by 7.7% and by 6.2% in comparison
Figure 4 (a) Individual serum insulin-time curves in 10 type 2 diabetic patients after test breakfast.
Therapeutic effects of psyllium
M Sierra
et al
837
European Journal of Clinical Nutrition
with phases 1 and 3, respectively. In the same way, LDL
cholesterol fell by 9.2 and 7.7%, respectively (significant dif-
ferences, Wilcoxon’s test). HDL cholesterol remained
unchanged during phase 2 (no significant differences, Fried-
man’s test, at P < 0.05). Psyllium administration also reduced
uric acid (10%, significant difference, Wilcoxon’s test).
Figure 4 (b) Individual serum insulin-time curves in 10 type 2 diabetic patients after test breakfast.
Therapeutic effects of psyllium
M Sierra
et al
838
European Journal of Clinical Nutrition
Finally, other variables, including potassium, calcium,
phosphorous, iron and vitamin A, showed no significant
changes during the three phases (no significant differences,
Friedman’s test, at P < 0.05). An increase in the levels of
magnesium and vitamin E was found when data of phases
2 and 3 were compared (significant differences, Wilcoxon’s
test). Sodium levels also showed an increase between phase 2
and phases 1 and 3 (significant difference, Wilcoxon’s test).
Discussion
As indicated by other authors (MacMahon & Carless, 1998;
Rodrı
´
guez-Mora
´
n et al, 1998; Oliver, 2000), in this study
psyllium was well tolerated without any significant adverse
effects.
The effects of sustained fibre supplementation on glycae-
mic control in subjects with diabetes mellitus have been
examined with considerable variations in results. The data
are somewhat difficult to evaluate because of differences in
population, fibre type, diet and study design (Weinstock &
Levine, 1988).
The effect of fibre is related to its viscosity (Jenkins et al,
1978) and with the method of administration (Wolever et al,
1991).
Rendell (2000) indicates that improvement in glucose
tolerance produced by consumption of viscous fibre is due
to slower absorption of carbohydrate rather than malabsorp-
tion. Intimate mixing, allowing physical interaction
between food and fibre, seems to be important in converting
the carbohydrate to what might be termed a slow-release
form.
Wolever et al (1991) demonstrated in normal and in type
2 diabetic patients that psyllium reduced the glycaemic
response to a flaked bran cereal test meal when the fibre
supplement was sprinkled onto the top of the cereal or
incorporated into the flakes, but not when it was taken
before the cereal. Despite this fact, in the present study the
fibre was taken dispersed in water because psyllium incor-
poration in a meal (by sprinkling it) would make it, in most
cases, unpalatable, and because this is the usual way any
patient would prepare an oral treatment with a therapeutic
fibre.
The mechanism of action of gel forming fibre is related to
the ability to increase the viscosity of the gastrointestinal
contents and thus interfere with motility and absorption
(Hopman et al, 1988). Several authors (Holt et al, 1979;
Sandhu et al, 1987) have demonstrated an inhibitory effect
of dietary fibre on gastric emptying, but others could not
prove it (Lawaetz et al, 1983; Lembcke et al, 1984). Hopman
et al (1988) showed that glucomannan affects absorption
within the intestine in a study carried out in patients with
previous gastric surgery, and this is in agreement with the
results obtained in several animal studies (Elsenhans et al,
1980,1981,1984; Johnson & Gee, 1981).
We found that psyllium, under the preparation used in
this study, decreased significantly postprandial blood glucose
concentrations in type 2 diabetic patients. It appears that
this fact can show the best effect of psyllium. Earlier studies
reported that psyllium reduced fasting serum glucose con-
centrations in individuals with type 2 diabetes (Fagerberg,
1982) and in type 2 diabetic patients with chronic portal-
systemic encephalopathy (Uribe et al, 1985). Other studies
demonstrated that different preparations of ispaghula husk
lowered postprandial serum glucose concentrations in type 1
(Florholmen et al, 1982), in type 2 diabetic patients (Sartor
et al, 1981; Pastors et al, 1991; Anderson et al, 1999), in
healthy volunteers (Sierra et al, 2001) and in both healthy
and type 2 diabetic subjects (Jarjis et al, 1984). Fibre doses
used were different, ranging from 3.6 g administered with
breakfast (Florholmen et al, 1982) to 35 g per day adminis-
tered as a dietary supplement (Uribe et al, 1985). In contrast,
no significant differences were found after a 50 g glucose load
Table 5 Minerals, vitamins and other biochemical parameters measured in 20 type 2 diabetic patients after a test
breakfast
Phase 1 Phase 2 Phase 3
x
¯
s.d. CV (%) x
¯
s.d. CV (%) x
¯
s.d. CV (%)
Uric acid (mmol=l)
a,b
0.33 0.08
c
24.2 0.30 0.07 24.7 0.33 0.07
c
22.4
Total cholesterol (mmol=l)
a,b
5.63 1.09
c
19.3 5.2 0.84 16.1 5.54 0.93
c
16.9
HDL cholesterol (mmol=l)
a,b
1.31 0.34 25.7 1.31 0.24 18.1 1.48 0.32
c
21.4
LDL cholesterol (mmol=l)
b
3.84 0.38
c
23.0 3.48 0.70 20.1 3.78 0.96 25.3
Ca (mmol=l)
b
2.38 0.10 4.4 2.34 0.11 4.5 2.35 0.08 3.4
P (mmol=l)
a,b
1.01 0.10 10.3 1.07 0.14 13.0 1.11 0.13 12.1
Na (mmol=l)
a,b
142.6 4.7
c
3.3 143.7 4.9 3.4 141.0 2.9
c
2.0
K (mmol=l)
a,b
4.6 0.4 9.1 4.4 0.4 9.2 4.3 0.4 8.6
Mg (mmol=l)
a,b
1.3 0.7 54.1 1.3 0.7 54.2 1.4 0.7
c
47.0
Fe (mmol=l)
b
15.2 4.14 27.2 15.0 3.94 26.3 16.9 5.28 31.3
Vitamin A (mmol=l)
b
2.44 0.35 21.5 2.09 0.70 26.9 2.79 0.72 27.0
Vitamin E (mmol=l)
a,b
36.7 9.98 27.2 39.2 9.13 23.3 44.3 9.12
c
20.6
a
Significant differences among phases (Friedman’s test,
P
< 0.05).
b
Significant differences among subjects (Friedman’s test,
P
< 0.05).
c
Significant differences with phase 2 (Wilcoxon modified test, for conditions see text).
Therapeutic effects of psyllium
M Sierra
et al
839
European Journal of Clinical Nutrition
administered with 3.5 or 7 g fibre to healthy subjects (Jarjis
et al, 1984).
The mean decrease of C
max
obtained in this study after the
administration of psyllium (10%) was similar to that
reported by Sartor et al (1981) after a standardized breakfast
(9%), and lower than the indicated by Pastors et al (1991) at
breakfast (14%) and at dinner (20%), and by Sierra et al
(2001) in healthy subjects after a glucose load (15.5%).
Results obtained with guar gum are variable. Several
authors report no modifications in glycaemia or a modest
improvement of glycaemic control (Botha et al, 1981; Car-
roll et al, 1981; Lim et al, 1990; Stahl & Berger, 1990), while
others indicate significant decreases (Smith & Holm, 1982;
Fuessl et al, 1987; Chuang et al, 1992; Fairchild et al, 1996;
Gatenby et al, 1996; Brenelli et al, 1997), some of them
similar to the value indicated in this paper (10.1%, Chuang
et al, 1992a, b) and others higher (50%, Fuessl et al, 1987;
35%, Brenelli et al, 1997).
In relation to insulin, the mean decrease we have found
when fibre is administered is not significant, although we
think that this may be due to the fact that patients had had
diabetes for different lengths of time. This result is similar to
that obtained by Jarjis et al (1984) in healthy and in type 2
diabetic volunteers. Pastors et al (1991) found significant
decreases for insulin after the administration of psyllium in
type 2 diabetic patients, with a reduction (12%) higher than
the reported in this study (5%). We have also found in a
previous study (Sierra et al, 2001) carried out in healthy
volunteers, a significant and higher reduction of insulin
concentrations (36.1%) after the administration of ispaghula
husk.
These differences observed in insulin concentrations after
the administration of psyllium, have also been reported with
guar gum: several authors found no significant (Groop et al,
1986,1993) or minimum (Stahl & Berger, 1990) changes
while others indicate significant differences (Chuang et al,
1992; Fairchild et al, 1996; Gatenby et al, 1996).
In relation to other parameters related to diabetes
(GhbA
1c
, fructosamine, C-peptide concentrations in blood
and in urine and glucose in urine), for all of them, we have
obtained a decrease in their concentrations in the presence
of fibre, which was significant for fructosamine. This last
fact is important because, due to the relatively short dura-
tion of this study, fructosamine is a better marker than
GhbA
1c
. This reduction might be due to psyllium’s ability
to reduce hunger feelings and energy intake (Rigaud et al,
1998). We have no data available from other authors about
how psyllium modifies these parameters. The results
obtained with other soluble fibres such as guar gum are
variable. Thus, Stahl and Berger (1990) found no significant
differences in glycosilated haemoglobin after the adminis-
tration of 15 g of guar gum daily during 3 months; Jones
et al (1985), after the administration of 10 g=day during 2
months, obtained a significant fall in GhbA
1c
levels, with-
out significant changes in 24 h urinary glucose excretion.
Behall (1990) observed that guar gum significantly reduced
blood C-peptide concentrations after the administration of
31.7 g fibre per day during 6 months and Holman et al
(1987) obtained no significant changes in blood C-peptide
and GhbA
1c
concentrations after the administration of
15 g=day during 8 weeks.
Mean reductions obtained in total and in LDL cholesterol
(7.7 and 9.2%, respectively, significant differences) were
slightly higher than those showed by Bell et al (1989) in
hypercholesterolaemic patients (4.8% reduction in total cho-
lesterol level and 8.2% in LDL cholesterol) after a treatment
with 10.2 g psyllium daily during 12 weeks. The reduction
observed for LDL cholesterol by Davidson et al (1998) in
hypercholesterolaemic patients after being treated with
10.2 g psyllium per day during 24 weeks was also slightly
lower (5.3%) than our value. On the other hand, our results
were slightly lower than those found by Anderson et al (1999)
in men with type 2 diabetes and hypercholesterolaemia after 8
weeks receiving 10.2 g psyllium daily. Romero et al (1998)
observed that LDL cholesterol concentrations were reduced
by an average of 22.6 and 26% after administering 1.3 g=day of
psyllium to healthy volunteers. In the same way, other authors
(Rodrı
´
guez-Mora
´
n et al, 1998; Segawa et al, 1998) found a
significant reduction in total and LDL cholesterol.
In relation to HDL cholesterol, we did not found significant
changes in this parameter after the administration of fibre.
Similar results were shown by other authors (Davidson et al,
1998; Romero et al, 1998). However, Rodrı
´
guez-Mora
´
n et al
(1998)observedasignificantincrease inthis parameterafterthe
administrationof 15 g psyllium dailytotype 2 diabeticpatients.
Results obtained with guar gum are, again, contradictory.
In this way, Jones et al (1985) found no changes in lipid
levels after the administration of this fibre, while other
authors obtained significant reductions in LDL cholesterol
concentrations without changes in HDL cholesterol
(Holamn et al, 1987) or with a significant decrease in total
cholesterol (Blake et al, 1997).
It has been suggested that deficiencies of calcium, iron,
trace metals, certain vitamins and possibly other nutrients
may occur after prolonged periods of high fibre intake
(Nuttall, 1983; American Diabetes Association, 1987).
The slight decrease observed in the mean level of uric acid
at the end of the psyllium phase in relation to the other two
phases is significant in both cases. We have no data obtained
by other authors for comparison and we think that further
studies are required in order to determine whether the use of
psyllium would be advantageous for the treatment of hyper-
uricaemic patients.
Results obtained in the present study on mineral and
vitamin levels indicate that psyllium does not significantly
modify serum concentrations when mean phase 2 values
were compared with those obtained in phase 1, except that
sodium increases significantly during the administration of
psyllium, although the differences in concentration are low.
We have no data available from other authors about how
psyllium modifies these parameters. Chuang et al (1992)
found that sodium, potassium, chloride, magnesium and
Therapeutic effects of psyllium
M Sierra
et al
840
European Journal of Clinical Nutrition
calcium levels showed no significant changes during the
treatment with guar gum (8 weeks).
Behall (1990) did not detect apparent changes in mineral
balance (calcium, magnesium, iron, copper and zinc), with
the exception of a negative manganese balance, after carbox-
ymethyl cellulose administration. In this study, carboxy-
methyl cellulose gum, karaya gum and locust bean gum
were consumed by the patients during 4 weeks each (19.5 g
of fibre per day). The author, in a second study (Behall et al,
1989), administered 31.7 g guar gum per day during 6
months and found that mineral balance was not affected
for iron, copper, zinc, calcium, manganese or magnesium.
Taking into account the results obtained in the present
study, those found in an earlier study carried out in healthy
subjects (Sierra et al, 2001) and according to Chuang et al
(1992), we conclude that psyllium treatment effectiveness
should be evaluated individually in each subject with the
purpose of establishing the most adequate dose and admin-
istration regime and a greater efficiency.
Acknowledgements
We wish to thank Madaus, S.A. Laboratory for the products
supplied and for their economic collaboration in this study,
the volunteers for their co-operation and Dr D Carriedo,
Head of Service of the Hospital de Leo
´
n, Dr JC Alvarez and
MA Gonzalez, members of the INSALUD Program for Dia-
betes Education and Control for their advice in the setting
up and execution of this study
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