In the absence of dietary surveillance, Chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects

Abstract

To investigate the effects of Absorbitol on body weight, anthropometry, body composition, blood pressures and lipid profiles in obese, hypercholesterolaemic subjects without dietary restriction.
A randomised, double blind. Placebo-controlled study.
Normal volunteers with no history of chronic illnesses (n=88) who were obese (body fat percentage > 20% in males and > 30% in females) and hypercholesterolaemic (total cholesterol > 5.20 mmol/L). Sixty-eight (72.3%) subjects completed the study.
After a 4 week run in phase, 4 placebo/Absorbitol (250 mg) capsules were prescribed 3 times a day before meals. Subjects received written information on healthy lifestyle but there was no dietary restriction or monitoring.
Weight, body mass index, lean body mass, waist, hip, blood pressure, fasting lipids and insulin levels were taken at baseline, 4th and 16th week of the study.
Analyses were on an intention-to-treat basis. Comparisons between groups were made using Student's t and Mann-Whitney tests for parametric and non-parametric data respectively.
There was no significant change in the measured parameters in Absorbitol treated subjects compared to those on placebo, with exception of HDL-cholesterol which increased in the absorbitol group and decreased in the placebo group (p=0.048). The side effects of Absorbitol were also comparable to that of placebo.
In the absence of dietary surveillance, Absorbitol does not bring about improvement in weight, anthropometry, body composition, blood pressure or lipid profile.

Full text

In the Absence of Dietary Surveillance,
Chitosan does not Reduce Plasma Lipids
or Obesity in Hypercholesterolaemic
Obese Asian Subjects
S C Ho, E S Tai, P H K Eng, C E Tan, A C K Fok
Department of
Endocrinology
Singapore General
Hospital
Outram Road
Singapore 169608
S C Ho, MBBS,
MMed (Singapore),
MRCP
Senior Registrar
E S Tai, MB.Ch.B,
MRCP, FAMS
Associate Consultant
P H K Eng, MBBS,
MRCP, FAMS
Consultant
C E Tan, MBBS,
MMed (Singapore),
FAMS
Consultant
A C K Fok, MBBS,
MMed (Singapore),
FAMS
Senior Consultant
Correspondence to:
Dr S C Ho
Tel: (65) 321 4654
Fax: (65) 227 3576
Singapore Med J 2001 Vol 42(1) : 006-010
O r i g i n a l A r t i c l e
ABSTRACT
Objective: To investigate the effects of Absorbitol
on body weight, anthropometry, body composition,
blood pressures and lipid profiles in obese,
hypercholesterolaemic subjects without dietary
restriction.
Design: A randomised, double blind. Placebo-
controlled study.
Subjects: Normal volunteers with no history of
chronic illnesses (n=88) who were obese (body fat
percentage > 20% in males and > 30% in females)
and hypercholesterolaemic (total cholesterol >
5.20mmol/L). Sixty-eight (72.3%) subjects completed
the study.
Intervention: After a 4 week run in phase, 4 placebo/
Absorbitol (250 mg) capsules were prescribed 3
times a day before meals. Subjects received written
information on healthy lifestyle but there was no
dietary restriction or monitoring.
Main outcome measures: Weight, body mass index,
lean body mass, waist, hip, blood pressure, fasting
lipids and insulin levels were taken at baseline, 4th
and 16th week of the study.
Statistical analysis performed: Analyses were on an
intention-to-treat basis. Comparisons between
groups were made using Student’s t and Mann-
Whitney tests for parametric and non-parametric
data respectively.
Results: There was no significant change in the
measured parameters in Absorbitol treated subjects
compared to those on placebo, with exception of
HDL-cholesterol which increased in the absorbitol
group and decreased in the placebo group (p=0.048).
The side effects of Absorbitol were also comparable
to that of placebo.
Conclusions: In the absence of dietary surveillance,
Absorbitol does not bring about improvement in
weight, anthropometry, body composition, blood
pressure or lipid profile.
Keywords: chitosan, Absorbitol, obesity, lipid profile,
diet
Singapore Med J 2001 Vol 42(1):006-010
INTRODUCTION
Chitosan, an non-acetylated or partially deacetylated
chitin (a linear homopolymer of β (1-4) linked N-
acetylglucosamine) can be found in the fungal cell wall
and the exoskeletons of various arthropods such as crabs
and shrimps
(l)
. It dissolves in the stomach to form an
emulsion with intra-gastric oil droplets, which then
precipitate in the small intestine at pH 6.0-6.5
(2,3)
. It
inhibits fat digestion by binding to the dietary lipid
present in the microemulsion and micelles present in
the small intestine
(4)
. Its ability to inhibit fat digestion
and absorption had been shown to be as effective as
cholestyramine in rats
(5)
.
Experiments in broiler chickens and rats fed chitosan
achieved a significant reduction in weight and
cholesterol levels
(6-9)
. Human studies had also shown that
chitosan produced significant decrease of weight and
cholesterol levels whist subjects were on a hypocaloric
diet of ~ 1000 kcal a
(10,11)
. Maezaki et al demonstrated a
cholesterol lowering effects of chitosan on 8 male adults
on 2549-2623 kcal a day diet
(12)
.
In Singapore, Absorbitol, a salt of chitosan,
(MinusFat, Ocean Healthcare Pte. Ltd.) is marketed as
a weight reducing agent and frequently used by the
general public without prior dietetic counselling. In
contrast to previous human studies that subjected
test individuals to hypocaloric diet, people taking
this compound in Singapore are not under strict
supervision and thus they have a more liberal caloric
intake. We undertook this study to investigate the
effects of Absorbitol on body weight, anthropometric
measurements, body composition, blood pressures and
lipid profiles in obese, hypercholesterolemic Asian
subjects while not on dietary surveillance.
METHODS
This was a randomised, double blind, placebo
controlled study. The ethics committee of Singapore

Singapore Med J 2001 Vol 42(1) : 007
General Hospital approved the study protocol. The
purpose of the study was explained and informed
consent was obtained from each subject. He/she was
allowed to withdraw from the trial at any point in time.
Normal volunteers were recruited from the general
public by advertisement. Only normoglycemic obese
individuals, defined as percentage body fat > 20% in
males and > 30% in females
(13)
, with total cholesterol
of > 5.20 mmol/L were enrolled in the study. Individuals
with seafood allergy, history of alcohol and drug usage,
chronic illnesses such as diabetes mellitus,
hypertension, ischemic heart disease, stroke, and
chronic liver or renal dysfunction were excluded.
The study spanned 16 weeks and subjects were
required to make 3 visits: at baseline, after 4 weeks
and at the end of 16 weeks. Each subject received brief
information from the physician and an educational
booklet regarding a healthy lifestyle and healthy diet
at the beginning of the study. During the run-in phase
comprising the first 4 weeks, all subjects were
prescribed placebo (450 mg cornstarch) identical to
Absorbitol capsules and instructed to take 4 capsules
3 times a day. This period was introduced to allow the
stabilization of any changes in the metabolic
parameters that occurred with lifestyle and dietary
modification. At the end of 4 weeks, subjects who met
the entry criteria were randomised to receive either
placebo or 4 capsules of absorbitol (257 mg Shellfish
L112 Absorbitol, 175 mg corn starch, 10 mg calcium
carbonate, 5 mg magnesium stearate) 3 times a day for
further 12 weeks.
For each visit, subjects were asked to attend an out
patient clinic after a 10-hour fast. They were advised
not to take any beverages containing alcohol or caffeine,
to abstain from exercising vigorously and drinking
excessive amount of water in the 12 hours prior to
attendance at the clinic.
Anthropometric measurements were taken
with the subjects in light clothing and without
shoes. Height was measured with a wall-mounted
stadiometer to the nearest 0.1 cm and weight was
measured to the nearest 0.1 kg on a digital scale
(SECA). Body mass index (kg/m
2
) was calculated
by dividing weight over height
2
. Waist and hip
circumferences were taken with a non-elastic tape
measure. The waist was defined as the narrowest
circumference between the costal margin and the
iliac crests and the hip as the widest circumference
between the waist and the thighs
(14,15)
.
Blood pressure was evaluated in the left arm in a
sitting position after a 5-minute rest. Two readings were
taken for each subject and the mean value used in the
analysis. Korotkov phase V was taken as the diastolic
blood pressure.
Bioelectric impedance analysis was performed with
a SEAC Bioimpedance meter (UniQuest Ltd., model
SFB3). This meter measures bioimpedance over the
frequency range of 4-1024 kHz using a tetrapolar
method. Fat free mass was calculated according to the
formula described by Lukaski et al
(16)
. Percentage body
fat was then derived from (weight - fat free mass) /
weight based on a 2-compartment model.
Any adverse reactions were determined by history
taking and compliance to treatment was monitored by
pill counting.
Venesection was performed at the end of each
visit for measuring lipid profile and fasting insulin.
Plasma glucose was assayed at the first visit to exclude
those with diabetes mellitus. The serum total
cholesterol, triglyceride, high density lipoprotein
(HDL) cholesterol and glucose were assayed by dry
chemistry with Kodak Ektachem Clinical Chemistry
Slides and read on the Kodak Ektachem 700 analyser
in the Biochemistry Department of the Singapore
General Hospital. Methods used were glucose
oxidase, O2 electrode for glucose; cholesterol oxidase
for total cholesterol; dextran sulphate and cholesterol
oxidase for HDL and lipase/glycerol kinase
calorimetric method without glycerol correction for
measurement of triglyceride, respectively. Insulin was
assayed by microparticle enzyme immunoassay
(Abbot Imx, Chicago, III).
Statistical Methods
Data were tested for normal distribution using the
Kolmogorov-Smirnov test. Comparisons between
groups were done using the Student’s T test for
normally distributed data and the Mann Whitney
rank sum test for non-parametric data. Results were
analysed on an intention-to-treat basis. All analyses
were 2-tailed with p-value of < 0.05 considered
statistically significant. All values were expressed as
mean + standard deviation unless otherwise stated.
Statistical analysis was performed using SPSS version
7.5 for Windows (SPSS Inc, Chicago, III).
RESULTS
A total of 88 subjects were enrolled in the study, of
which 85 (96.6% of the cohort enrolled) returned for
their 2
nd
visit and analyses of results were performed
with the final 68 subjects (72.3% of cohort enrolled)
who completed the entire project. Among the 31
females, 15 subjects were assigned to placebo and 16
were given Asorbitol treatment. In the male group, 17
subjects received placebo and 20 received Asorbitol.
Baseline characteristics of treatment and placebo
groups at the beginning of the study are shown in
table I. In the female cohort, the Asorbitol treated

008 : 2001 Vol 42(1) Singapore Med J
group had significantly higher waist-hip ratios than
the placebo treated group (p=0.046) whereas in the
male cohort, the Asorbitol treated group had a lower
percentage body fat compared to the placebo group at
the start of the trial (p=0.044).
Table II shows the change in measured variables
during the treatment period. The change in each
parameter was obtained by subtracting results of the 2
nd
visit from the 3
rd
visit. The change was positive if there
had been a rise and negative if there had been decline
in the measure parameter. The change in HDL-
cholesterol in male subjects in placebo and absorbitol
groups were significantly different (p=0.048). This
difference was due to a small increase (0.07) In HDL-
cholesterol in men on absorbitol and a small decrease
in HDL-cholesterol level (0.04 mmol/1) in those on
placebo. When each group is taken on its own, there is
no significant change in HDL-cholesterol from the
baseline. A similar pattern in women but this did not
reach statistical significance.
Compliance with the prescribed therapy was generally
good with no significant difference between the placebo
and absorbitol groups. Percentage of drug consumed was
70.4% + 7.5 and 82.6% + 3.3 among males taking placebo
and absorbitol respectively. The equivalent figures for
females were 78.6% + 6.4 and 78.6% + 4.7.
Out of 85 subjects who returned for the second
visit, data on side effects were available from 76
individuals. 13 (17.1%) subjects reported adverse
effects from the treatment prescribed. The most
frequent complaints were gastro-intestinal (5 receiving
placebo and 7 receiving absorbitol) and included
epigastric discomfort, constipation, diarrhoea, nausea
and dryness of throat. 1 placebo treated subject
reported the occurrence of a non-specific macular rash.
The prevalence of side effects reported were not
significantly different between the groups (p=0.53).
12 female and 8 male subjects defaulted follow up.
Their baseline characteristics (data not shown) were
similar to subjects in the placebo and Asorbitol groups
except for age. Those that defaulted were younger
(age 36.8 + 8.5.p = 0.003).
DISCUSSION
While animal experiments have shown weight
reducin g and hy pocholest erolem ic effects of
chitosan
(6-9)
, most human studies demonstrated
similar success only in in dividu als given a
hypocaloric diet of about 1000 kcal
(10,11)
. Maezaki et
al reported cholesterol-lowering effect of chitosan
in 8 adult males with daily intake of 2549-2623
kcal
(12)
. Hitherto, no study has involved free-living
Table I. Baseline characteristics of subjects in treatment and placebo groups.
Female Male
Parameters Absorbitol Placebo Absorbitol Placebo
Mean + SD
Age (year) 42.8 + 6.0 44.3 + 8.1 42.4 + 7.3 42.5 + 7.5
Weight (kg) 63.9 + 9.0 60.0 + 9.5 75.1 + 11.2 77.1 + 11.1
BMI (kg/m
2
) 25.6 + 2.6 24.6 + 3.3 25.7 + 3.6 27.0 + 3.4
Lean mass (kg) 41.1 + 7.1 38.4 + 4.4 55.7 + 8.2 54.4 + 7.8
Fat mass (kg) 22.8 + 4.1 21.6 + 6.3 19.4 + 5.0 22.8 + 6.5
Fat percentage 35.8 + 4.4 35.5 + 5.2 25.7 + 4.4 29.3 + 5.8*
Waist (cm) 80.6 + 6.9 76.4 + 8.3 87.9 + 8.2 90.6 + 8.0
Hip (cm) 99.6 + 6.2 98.8 + 6.7 99.7 + 6.5 102.0 + 6.2
Waist-hip ratio 0.81 + 0.05 0.77 + 00.5* 0.88 + 0.03 0.89 + 0.05
Systolic BP (mmHg) 109.9 + 18.6 109.0 + 14.3 117.5 + 16.0 118.2 + 13.1
Diastolic BP (mmHg) 74.0 + 6.9 74.0 + 6.1 83.5 + 11.4 80.4 + 11.4
Total cholesterol (mmol/L) 6.22 + 0.87 6.37 + 0.77 6.02 + 0.58 6.56 + 1.77
HDL-cholesterol (mmol/L) 1.30 + 0.29 1.44 + 0.49 1.21 + 0.29 1.11 + 0.35
LDL-cholesterol (mmol/L) 4.22 + 0.86 4.13 + 0.82 3.92 + 0.60 4.18 + 0.84
Triglyceride (mmol/L) 1.53 + 0.72 2.14 + 2.83 2.07 + 0.87 2.58 + 1.54
Fasting insulin (mU/L) 10.9 + 6.7 9.0 + 4.7 10.1 + 6.5 11.8 + 4.4
BMI body mass index
BP blood pressure
HDL high density lipoprotein
LDL low density lipoprotein
* p<0.05 Student’s test

Singapore Med J 2001 Vol 42(1) : 009
males and females. While the authors recognise the
importance of diet in the modulation of body weight and
lipid profile, this product is often purchased by individuals
over the counter without a medical prescription for
purpose of weight reduction without prior dietary
counselling or subsequent monitoring. In light of this,
we only counselled the subjects on healthy lifestyle and
diet once and deliberately omitted nutritional
surveillance throughout the study period to reflect the
actual circumstances in which these products are used.
The cohort of subjects in our study were more obese
and had higher lipid profiles than national average
(National Health Survey 1992, data unpublished). It was
thus very likely that their daily calorie and fat intake
exceeded the national average (1673 kcal and 56 g fat
for women and 2283 kcal and 78 g fat for men - National
Health Survey 1992).
This study did not show any significant change
in weight, anthropometric measurement, body
composition, blood composition, blood pressure, lipid
profile or fasting insulin levels in subjects treated with
Asorbitol compared to the placebo treated group. We
believe that subjects could have inadvertently
increased their calorie intake under the false belief
that chitosan would bind all fat that was consumed.
Any beneficial effects of chitosan would then be
masked by the dietary indiscretion. The fall in HDL-
cholesterol among men taking placebo and the
Table II. Changes in the parameters of subjects during the treatment phase.
Female Male
Parameters Absorbitol Placebo P Absorbitol Placebo P
Mean + SD
Weight (kg) 0.03 + 1.54 0.26 + 1.21 NS -0.51 + 1.79 -0.44 + 0.99 NS
BMI (kg/m
2
) 0.00 + 0.63 0.11 + 0.49 NS -0.18 + 0.64 -0.15 + 0.34 NS
Lean mass (kg) 0.60 +1.75 -0.02 + 1.16 NS
♦
-0.42 + 2.17 -0.63 + 2.58 NS
♦
Fat mass (kg) -0.57 + 1.76 0.27 +1.43 NS -0.08 + 1.76 0.19 + 2.21 NS
Fat percentage -0.95 + 2.43 0.24 + 2.13 NS
♦
-0.07 + 2.19 0.34 + 2.91 NS
♦
Waist (cm) 0.84 + 1.49 0.24 + 2.19 NS
♦
0.15 + 1.85 -0.01 + 1.95 NS
♦
Hip (cm) 0.03 + 2.59 -0.09 + 2.96 NS
♦
0.01 + 2.07 -0.58 + 1.88 NS
♦
Waist-hip ratio 0.009 + 0.018 0.002 + 0.027 NS 0.001 + 0.019 0.005 + 0.023 NS
Systolic BP (mmHg) 2.4 + 11.5 2.4 + 14.7 NS
♦
-0.6 + 9.5 1.3 + 11.3 NS
Diastolic BP (mmHg) 0.2 + 10.2 -0.5 + 8.0 NS -1.0 + 11.0 -1.2 + 12.2 NS
Total cholesterol (mmol/L) -0.12 + 0.58 -0.20 + 0.35 NS 0.14 + 0.51 -0.08 + 0.50 NS
HDL-cholesterol (mmol/L) 0.06 + 0.29 -0.12 + 0.32 NS
♦
0.07 + 0.22 -0.04 + 0.09 P<0.05
LDL-cholesterol (mmol/L) -0.11 + 0.45 -0.06 + 0.44 NS -0.05 + 0.10 -0.02 + 0.44 NS
Triglyceride (mmol/L) -0.01 + 1.09 0.15 + 0.68 NS -0.11 + 1.03 0.14 + 0.73 NS
Insulin (mU/L) 0.44 + 5.36 -0.65 + 3.37 NS 2.70 + 11.59 1.48 + 2.77 NS
Unless otherwise indicated, Student’s test was used
♦
Mann Whitney test
NS not significant
improvement in those on absorbitol is consistent with
this hypothesis.
Non-compliance to therapy might also have
contributed to the results shown. Compliance was
monitored by the percentage of capsules consumed.
In the Asorbitol group, compliance was 82.6% in
females and 78.6% in males during the treatment
period of 12 weeks. This reflected an average dose of
2.48 g and 2.36 g Asorbitol a day in females and males
respectively. The study reported by Maezaki et al had
used 3-6 g of chitosan a day to demonstrate beneficial
effects on the metabolic parameters. Our group of
patients in contrast, had received a smaller dose that
might be sub-therapeutic and therefore accounted for
the drug failure.
While Asorbitol might not have brought about
metabolic improvements in the subjects, the treatment
was well tolerated and the incidences of side effects
were similar between placebo and treated group.
CONCLUSIONS
To achieve weight loss and cholesterol reduction, dietary
restriction remains a cornerstone of therapy. While we
believe that there may be some benefit of chitosan in
achieving weight loss and cholesterol lowering, our study
demonstrates that, in the absence of dietary surveillance,
chitosan does not bring about improvements in weight,
body composition or lipid profile.

010 : 2001 Vol 42(1) Singapore Med J
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Vascular Workshop
About the Workshop:
It brings the surgeon step-by-step from mounted specimens to the live animal practice where
vascular control and suturing are done under the most realistic conditions available. At the end of
the workshop, the surgeon should be able to approach an artery or vein with greater sense of
familiarity and confidence.
Date/Time:
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8.30 am to 5 pm hours
Venue:
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Department of Experimental Surgery
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Closing date for registration:
16 April 2001
Payment for registration of the Vascular Workshop:
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SGH Postgraduate Medical Institute
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