Chinese Medicine, 2011, 2, 125-129
doi:10.4236/cm.2011.24021 Published Online December 2011 (http://www.SciRP.org/journal/cm)
Copyright © 2011 SciRes. CM
Bitter Melon (Momordica Charantia) Reduces Serum
Sialic Acid in Type2 Diabetics: Evidence to
Delay the Process of Atherosclerosis
Inayat Ur Rahman1*, Mohammad Bashir2, Mohammad Salman2, Mohammad Idrees3,
Mohammad Iqbal Khan4
1Gandhara College of Pharmacy, Gandhara University, Peshawar, Pakistan
2Institute of Medical Science, Kohat University of Science & Technology, Kohat, Pakistan
3Departmen t o f Pathology, Khyber Medical College, Peshawar, Pakistan
4Department of Chemistry, Kohat University of Science & Technology, Kohat, Pakistan
E-mail: *firstname.lastname@example.org, mbashir@yaho o.com, email@example.com
Received February 7, 2011; revised April 3, 2011; accepted November 17, 2011
More than 1000 herbal products have been used by diverse cultures of the world to treat hyperglycemia and
among them bitter melon (Momordica charantia) is one of the most popular herbal resource. The beneficial
effects of bitter melon is not limited to hypoglycaemia only, but it also ameliorates diet induced obesity, in-
sulin resistance and exhibit cardioprotective effects. The present study attempts to investigate the effect of
bitter melon fruit juice on a newly investigated risk factor, sialic acid in type2 diabetics. A total of 40 type2
diabetic patients, divided into group A (n = 20) and group B (n = 20) were investigated during the present
study. The patients of group A were following bitter melon fruit juice treatment along with diet control,
whereas the patients of group B were on diet control only. Serum sialic acid (SSA) decreased in group A
from 66.20 ± 2.30 mg/dl to 63.50 ± 2.10 mg/dl (<0.11) but, increased in group B from 66.50 ± 1.70 mg/dl to
68.20 ± 2.50 mg/dl (<0.12), compared to baseline. Post-treatment between group comparison revealed a sig-
nificant difference (<0.05). The beneficial effects on fasting plasma glucose (FPG) and glycohemoglobin
(HbA1-c) were also greater in group A compared to group B as was the case with blood lipids, weight and
blood pressure. The study provides another mechanism for the cardioprotective effect of bitter melon and
further strengthens its value in the management of type2 diabetes.
Keywords: Sialic Acid, Type2 Diabetes Mellitus, Bitter Melon, Cardiovascular Disease
Plant medicines have a long history of use in various
pathological conditions. Bitter melon (Momordica cha-
rantia) is traditionally used for treating diabetes in deve-
loping world including India and Pakistan, which have a
long history of the use of herbal remedies in diabetes .
Bitter melon is a traditional plant used by ayurvedic
doctors of medicines to benefit various conditions inclu-
ding diabetes . The effect of bitter melon on various
diabetes associated cardiovascular risk factors like plas-
ma lipids, obesity and insulin resistance is known [3,4]
and the present study is designed to determine the effect
of bitter melon on a recently investigated cardiovascular
(CV) risk marker/factor, sialic acid. Sialic acid is used to
be a group name for acetylated derivatives of neuraminic
acid and the serum level of it is increased in type2 dia-
betes mellitus [5-8]. The mechanistic aspect of raised le-
vels of serum sialic acid (SSA) is not very clear, but
several possibilities have been suggested for elevated
levels in diabetic patients. There may be generalized en-
dothelial cell dysfunction or macrovascular disease, eith-
er through loss of sialic acid containing glycoproteins
from vascular cells into blood stream or through an acute
phase response. Circulating sialic acid is mostly cova-
lently attached to glycoproteins, particularly the acute
phase group. Type2 diabetes mellitus may be considered
an acute phase disease, since in type2 diabetes (not type1
diabetes), even without tissue complications, the serum
levels of acute phase proteins, C-reactive protein and ha-
I. UR RAHMAN ET AL.
ptoglobin are elevated [9-13].
There may be increased sialylation of serum proteins
 or reduction in desialylation of plasma glycoproteins
. Alternatively or in addition, declining renal func-
tion in diabetes may retard the excretion of acute phase
proteins or other sialic acid containing proteins, leading
to high SSA levels . Recent studies indicate a posi-
tive association between SSA and cardiovascular mor-
tality and has been proposed to be a long term predictor
of coronary artery disease in adults, particularly women
The evidence of raised level of SSA as a risk factor for
cardiovascular disease (CVD) signifies the importance of its
status in diabetes mellitus. Therefore, the present study was
carried out to test our hypothesis that bitter melon induced
reduction in blood glucose and blood lipids are associated
with changes (reduction) in SSA in type2 diabetics.
2. Materials and Methods
2.1. Study Design
A total of 40 recently diagnosed type2 diabetic patients at-
tending Afghan Dawakhana, Lakki Marwat, were investi-
gated during the present study. They were divided into two
groups, A and B. The patients in group A (20) were on diet
control only, whereas, the patients in group B (20) were also
taking freeze-dried bitter melon juice in a dose of 1 g/d
along with diet control. The volunteer patients of type2 dia-
betes were explained the research protocol and their written
informed consents obtained for the study. Participants were
informed of their right to withdraw from the study at any
time. The study was conducted for a period of 12 weeks.
Therapeutic goal was to achieve FPG level <140 mg/dl,
while observing the changes in SSA.
2.2. Procedures and Measurements
Fasting blood samples were collected after 12 - 14 h
overnight fast without the use of a tourniquet. Metabolic
variables were determined at baseline and at the end of
the study period.
Sialic acid was determined by using a method pro-
posed by Shamberger . In brief, sialic acid in the
sample reacts with Ehrlich’s reagent and this result in the
formation of a white precipitate. After incubation in wa-
ter bath the colour of the mixture turned blue from white.
Sodium chloride was added to the mixture and centrifu-
ged. The intensity of the colour of supernatant is directly
proportional to the concentration of sialic acid and is
read in a spectrophotometer at 525 nm.
Fasting plasma glucose (FPG), glycohemoglobin (Hb-
A1-c), total cholesterol (TC), high density lipoprotein
cholesterol (HDL-c), low density lipoprotein cholesterol
(LDL-c) and triglyceride (TG) levels were analyzed by
enzymatic methods, using commercially available kits.
SSA, HbA1-c and blood lipids were determined at
start and at the end of the study period whereas FPG was
determined at start and then after every 2 weeks.
Standing height and weight were measured with the
subjects in light clothing and without shoes. Height was
recorded to the nearest centimetre and weight to the nea-
rest 0.1 Kg. The weighing scales (Detecto-Medic, NY,
USA) were standardized on each visit using standard
weights of 20 and 70 Kg. Body mass index (BMI), defi-
ned as weight in Kg/height (in meters) squared was cal-
culated, and used as an index for obesity. Obesity was
defined according to the WHO standards as BMI <30
. Blood pressure was measured according to a stan-
dard protocol . Hypertension was defined as systolic
blood pressure 160 mmHg and/or diastolic blood pres-
sure 95 mmHg and/or current history of antihypertensive
medications, according to the WHO criteria .
2.3. Source and Preparation of Bitter Melon
Momordica charantia (family Cucurbitaceae, commonly
known as Ku gua, bitter melon, karela or bitter gourd)
was purchased from a local market in Khyber Pukh-
toonkhwa Province, Pakistan and authenticated by a pha-
rmacognosy expert before juice preparation. The juice
was prepared by the method proposed by Chen et al. .
Unripe bitter melon fresh fruit was washed thoroughly
with water, cut open and the seeds removed. The juice
was extracted from the edible portion by crushing the
fruit in electric juicer (NOVA-Osaka, Japan) and strain-
ing through a muslin cloth. The yield was 390 ml/Kg.
The juice was frozen and then completely lyophilized by
continuous freeze drying operation for 72 h (Dura Bulk
Tray Dryer, FTS System, Stone Ridge, NY). The yield
was 7 g powder/Kg of fresh fruit. The powder was filled
in hard gelatine capsules in a dose of 0.5 g and 1 g.
Results are expressed as means ± SD. Data were ana-
lysed using the Statistical Package for Social Sciences,
SPSS (SPSS Inc., Chicago, IL, USA) and a P ≤ 05 was
taken as the cut-off level for significance. Because the
distribution of most variables was not symmetric, we
used non-parametric statistical methods. The Mann-Wh-
itney U-test was used for between group comparisons
and Kruskal-Wallis one-way ANNOVA test was used for
comparisons involving more than two groups.
Table 1 shows baseline characteristics of the study groups.
Copyright © 2011 SciRes. CM
I. UR RAHMAN ET AL.
There were no significant differences of metabolic vari-
ables among the groups. Table 2 shows the post-treat-
ment values of metabolic variables. Serum sialic acid
(SSA) showed a trend towards decrease in group A from
66.20 ± 2.30 mg/dl to 63.50 ± 2.10 mg/dl (<0.11)
whereas, increased in group B from 66.50 ± 1.70 mg/dl
to 68.20 ± 2.50 mg/dl (<0.12). Post-treatment between
group comparisons revealed a significantly high SSA in
group B (Figure 1).
Fasting plasma glucose (FPG) decreased to <140
mg/dl within the first month of study in both group A
and group B. After that, the level deteriorated (≥140
mg/dl) more rapidly in group B than group A (Figure 2).
HbA1-c significantly decreased in both group A and gr-
oup B, compared with baseline (Table 2).
Table 1. Baseline characteristics of group A and group B.
Variable Group A Group B
N 20 20
Age (y) 52 ± 3.40 52.20 ± 4.70
Sex (M/F) 8/12 9/11
BMI (Kg/m2) 26 ± 2.20 26.70 ± 2.80
Weight (Kg) 77.60 ± 4.30 77 ± 4.40
SBP (mmHg) 139 ± 6 138 ± 5
DBP (mmHg) 94 ± 3 95 ± 3
Smoking (cig/d) 8 10
SSA (mg/dl) 66.20 ± 2.30 66.50 ± 1.70
FPG (mg/dl) 151 ± 6.20 148 ± 6.80
HbA1-c (%) 8.60 ± 0.40 8.70 ± 0.50
TC (mg/dl) 196.30 ± 6.10 194 ± 5.60
HDL-c (mg/dl) 49.20 ± 2.90 48.40 ± 1.50
LDL-c (mg/dl) 150.20 ± 4.20 151.30 ± 3.50
TG (mg/dl) 172.90 ± 5.10 172.40 ± 3.60
Data are mean ± SD; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pres-
sure; SSA: Serum Sialic Acid; FPG: Fasting Plasma Glucose; HbA1-c: Glyco-
hemoglobin; TC: Total Cholesterol; HDL-c: High Density Lipoprotein choles-
terol; LDL-c: Low Density Lipoprotein cholesterol; TG: Triglyceride.
SSA (mg/d l)
Figure 1. Comparison of baseline and post-treatment SSA
in group A and group B.
Figure 2. Changes in FPG overtime.
Table 2. Post-treatment biochemical profile of group A and
Group A Group B
SSA (mg/dl)63.50 ± 2.10<0.11 68.20 ± 2.50<0.12
FPG (mg/dl)142 ± 3.10 <0.05 142.70 ± 5.60≤0.05
HbA1-c (%)7.50 ± 0.30 <0.01 7.50 ± 0.60 <0.02
TC (mg/dl)187.30 ± 5.90<0.05 198.30 ± 8.70<0.07
(mg/dl) 53 ± 5.30 <0.12 51.30 ± 4.50<0.18
(mg/dl) 144.10 ± 5.20<0.05 154.70 ± 7.10<0.12
TG (mg/dl)170.50 ± 8.80<0.24 171.40 ± 7.50<0.20
Weight (Kg)75.50 ± 4.50<0.13 77.90 ± 4.30<0.19
(mmHg) 137 ± 5.10 <0.19 139 ± 6.70 <0.20
(mmHg) 92 ± 6.70 <0.22 97 ± 4.10 <0.21
Changes occurred in blood lipids during the study pe-
riod are given in Table 2. Total cholesterol (TC) chan-
ged by −9 mg/dl and +4.30 mg/dl in group A and group B
respectively. High density lipoprotein cholesterol (HDL-c)
changed by +3.80 mg/dl and +2.90 mg/dl. Low density
lipoprotein cholesterol (LDL-c) changed by −6.10 mg/dl
and +3.40 mg/dl. Triglyceride (TG) changed by −2.40
mg/dl and −1 mg/dl in group A and group B respectively.
Weight (Kg) decreased by −2.10 in group A and in-
creased by +0.90 in group B. Both systolic and diastolic
blood pressure (SBP and DBP) decreased in group A by
−2 mmHg each, whereas increased by +1 mmHg and +2
mmHg in group B respectively (Table 2).
Diabetes is the metabolic syndrome associated with both
Copyright © 2011 SciRes. CM
I. UR RAHMAN ET AL.
microvascular and macrovascular complications and am-
ong these cardiovascular complications is the main cause
of death in such patients . Therefore modulation of
the cardiovascular risk factors will definitely prove help-
ful to reduce the incidence of cardiovascular complica-
tions in these patients. Results of the present study sug-
gest that the use of bitter melon in type2 diabetes de-
creases the SSA level thereby indicating the usefulness
of bitter melon in protecting against CV complications in
diabetes. Lindberg et al.  have shown that the pre-
dicting power of sialic acid for coronary heart disease is
more or of the same magnitude to that of cholesterol.
Recent studies also indicate sialic acid as an independent
risk factor for cardiovascular disease  and thus any
positive change (decrease) in SSA may lead to control
and deceleration of atherosclerotic process. Indeed, a sig-
nificant decrease in SSA levels in growth hormone defi-
cient patients after receiving growth hormone therapy
has been related to the prognostic effect of this hormone
in groups at risk of cardiovascular disease .
There may be several reasons for beneficial effects of
bitter melon on SSA including, the inhibitory effect on
glycation of LDL-c , protecting the biological sys-
tems from potentially harmful effects of free radicals due
to antioxidant properties [27,28], reduces adiposity and
exerts antihyperlipidemic effects [29,30]. A positive as-
sociation between SSA, blood lipids and BMI have been
reported . The role of bitter melon in protecting ag-
ainst cardiovascular complications of diabetes has been
reported previously [32,33] and a decrease in SSA shown
in this study is the novel finding because it is an indica-
tive of a decrease in the development and progression of
 J. H. McNeill, “Experimental Models of Diabetes,” 1st
Edition, CRC Press, Boca Raton, 1999.
 E. Basch, S. Gabardi and C. Ulbricht, “Bitter Melon
(Momordica Charantia): A Review of Efficacy and
Safety,” American Journal of Health-System Pharmacy,
Vol. 60, No. 4, 2003, pp. 356-359.
 J. K. Grover and S. P. Yadav, “Pharmacological Actions
and Potential Uses of Momordica Charantia, a Review,”
Journal of Ethnopharmacology, Vol. 93, No. 1, 2004, pp.
 P. Chaturvedi, “Role of Momordica Charantia in Main-
taining the Normal Levels of Lipids and Glucose in Dia-
betic Rats Fed a High-Fat and Low-Carbohydrate Diet,”
British Journal of Biomedical Science, Vol. 62, No. 3,
2005, pp. 124-126.
 J. C. Pickup, M. B. Mattock, M. A. Crook, et al., “Serum
Sialic Acid Concentration and Coronary Heart Disease in
NIDDM,” Diabetes Care, Vol. 18, No. 8, 1995, pp.
 J. C. Pickup, G. A. Roberts, A. M. Kehley, et al., “Higher
Serum Sialic Acid in Women than in Men with NIDDM:
Possible Relevance to Cardiovascular Risk in NIDDM
Women,” Diabetes Care, Vol. 20, 1997, p. 1494.
 V. Vijay, C. Snehalatha, A. Ramachandran and M.
Jayaraman, “Serum Sialic Acid in South Indian Type2
Diabetic Patients with Microvascular Complications,”
Diabetic Medicine, Vol. 15, No. 2, 1998, p. 176.
 N. Abdella, A. O. Akanji, O. A. Mojiminiyi, et al., “Rela-
tion of Serum Total Sialic Acid Concentrations with
Diabetic Complications and Cardiovascular Risk Factors
in Kuwaiti Type2 Diabetic Patients,” Diabetes Research
and Clinical Practice, Vol. 50, No. 1, 2000, pp. 65-72.
 M. Crook, P. Tutt, H. Simpson and J. C. Pickup, “Serum
Sialic Acid and Acute Phase Proteins in Type1 and Type2
Diabetes Mellitus,” Clinica Chemica Acta, Vol. 219, No.
1-2, 1993, pp. 131-138.
 K. Taniuchi, K. Chifu, N. Hayashi, et al., “A New Enzy-
matic Method for the Determination of Sialic Acid and Its
Application as a Marker of Acute Phase Reactants,” Kobe
Journal of Medical Sciences, Vol. 27, 1981, pp. 91-102.
 D. Thompson, S. P. Hrrison, S. W. Evans and J. T.
Whicher, “Insulin Modulation of Acute Phase Protein
Production in a Human Hepatoma Cell Line,” Cytokine,
Vol. 3, No. 6, 1991, pp. 619-626.
 M. Haq, S. Haq, P. Tutt and M. Crook, “Serum Total
Sialic Acid and Lipid Associated Sialic Acid in Normal
Individuals and Patients with Myocardial Infarction and
Their Relationship to Acute Phase Proteins,” Annals of
Clinical Bioche mi str y, Vol. 30, 1993, pp. 383-386.
 S. P. Campos and H. Baumann, “Insulin Is a Prominent
Modulator of the Cytokine Stimulated Expression of
Acute Phase Plasma Proteins,” Molecular and Cellular
Biology, Vol. 12, 1992, pp. 1789-1797.
 M. D. Flynn, R. J. M. Corrall, P. J. Waters and C. A.
Pennock, “Sialic Acid and Cardiovascular Mortality,”
British Medical Journal, Vol. 302, 1991, pp. 533-534.
 A. G. Morell, G. Gregoriadis, I. H. Scheinberg, et al.,
“The Role of Glycoproteins in the Circulation,” The
Journal of Biological Chemistry, Vol. 246, 1971, pp.
 M. A. Crook, K. Earle, A. Morocutti, et al., “Serum Sialic
Acid, a Risk Factor for Cardiovascular Disease, Is In-
creased in IDDM Patients with Microalbuminuria and
Clinical Proteinuria,” Diabetes Care, Vol. 17, No. 4,
1994, pp. 305-309. doi:10.2337/diacare.17.4.305
 A. Vaya, C. Falco, E. Reganon, et al., “Influence of
Plasma and Erythrocyte Factors on Red Blood Cell Ag-
gregation in Survivors of Acute Myocardial Infarction,”
Thromb Haemostas, Vol. 91, 2004, pp. 354-359.
Copyright © 2011 SciRes. CM
I. UR RAHMAN ET AL.
Copyright © 2011 SciRes. CM
 R. J. Shamberger, “Serum Sialic Acid in Normal and
Cancer Patients,” Journal of Clinical Chemistry & Clini-
cal Biochemistry, Vol. 22, 1984, pp. 64-67.
 World Health Organization, “Diet, Nutrition and the Pre-
vention of Chronic Diseases,” Report of a WHO Study
Group, Technical Report Series 1990, No. 797, World
Health Organization, Geneva, 1990.
 J. D. Cohen, R. H. Grimm and W. M. Smith, “The Multi-
ple Risk Factor Intervention Trial (MRFIT) 4: Interven-
tion on Blood Pressure,” Preventive Medicine, Vol. 10,
No. 4, 1981, pp. 501-518.
 World Health Organization Expert Committee, “Arterial
Hypertension,” Technical Report Series, No. 628, WHO,
 A. D. Paterson, B. N. Rutledge, P. A. Cleary, et al., “The
Effect of Intensive Diabetes Treatment on Resting Heart
Rate in Type1 Diabetes: The Diabetes Control and Com-
plications Trial (DCCT), Epidemiology of Diabetes In-
terventions and Complications Study,” Diabetes Care,
Vol. 30, No. 8, 2007, pp. 2107-2112.
 G. Lindberg, L. Rastam, B. O. Gullber and G. A. Eklund,
“Serum Sialic Acid Concentration Predicts Coronary
Heart Disease and Stroke Mortality: Multivariate Analy-
sis Including 54385 Men and Women during 30.5 Years
Follow-up,” International Journal of Epidemiology, Vol.
21, No. 2, 1992, pp. 253-257.
 M. W. Knuiman, G. F. Watts and M. L. Divitini, “Is
Sialic Acid an Independent Risk Factor for Cardiovascu-
lar Disease: A 17 Year Follow-up Study in Busselton,
Western Australia,” Annals of Epidemiology, Vol. 14, No.
9, 2004, pp. 627-632.
 M. Pfeifer, R. Verhovee, B. Zizek, et al., “Growth Hor-
mone Reverses Early Atherosclerotic Changes in Growth
Hormone Deficient Adults,” The Journal of Clinical En-
docrinology & Metabolism, Vol. 84, No. 2, 1999, pp.
 C. L. Hsieh, Y. C. Lin, W. S. Ko, et al., “Inhibitory Effect
of Some Selected Nutraceutic Herbs on LDL Glycation
Induced by Glucose and Glyoxal,” Journal of Ethno-
pharmacology, Vol. 102, No. 3, 2005, pp. 357-363.
 N. M. Ansari, L. Houlihan, B. Hussain and A. Pieroni,
“Antioxidant Activity of Five Vegetables Traditionally
Consumed by South-Asian Migrants in Bradford, York-
shire, UK,” Phytotherapy Research, Vol. 19, No. 10,
2005, pp. 907-911. doi:10.1002/ptr.1756
 D. M. Lee, W. H. Hoffman, G. F. Carl, et al., “Lipid
Peroxidation and Antioxidant Vitamins Prior to, during,
and after Correction of Diabetic Ketoacidosis,” Journal
of Diabetes and Its Complications, Vol. 16, No. 4, 2002,
pp. 294-300. doi:10.1016/S1056-8727(01)00215-X
 L. L. Chan, Q. Chen, A. G. G. Go, E. K. Y. Lam and E. S.
T. Li, “Reduced Adiposity in Bitter Melon (Momordica
Charantia)-Fed Rats Is Associated with Increased Lipid
Oxidative Enzyme Activities and Uncoupling Protein
Expression,” Biochemical and Molecular Actions of Nu-
trients, Vol. 135, No. 11, 2005, pp. 2517- 2523.
 I. Ahmad, M. S. Lakhani, M. Gillett, et al., “Hypo-
triglyceridemic and Hypocholesterolemic Effects of
Antidiabetic Momordica Charantia (Karela) Fruit Extract
in Streptozotocin Induced Diabetic Rats,” Diabetes Re-
search and Clinical Practice, Vol. 51, No. 3, 2001, pp.
 M. Crook, P. Lumb, V. Andrews and R. Swaminathan,
“Serum Total Sialic Acid, a Reputed Cardiovascular Risk
Factor, and Its Relationship to Lipids, Plasma Fasting In-
sulin, Blood Pressure and Body Mass Index in Normal
Individuals,” Clinical Science, Vol. 95, 1998, pp. 53-57.
 S. S. Dhanasekar and S. Subramanian, “Antioxidant
Properties of Momordica Charantia (Bitter Gourd) Seeds
on Streptozotocin Induced Diabetic Rats,” Asia Pacific
Journal of Clinical Nutrition, Vol. 14, No. 2, 2005, pp.
 R. Gebhardt, “Antioxidative, Antiproliferative and Bio-
chemical Effects in HepG2 Cells of a Homeopathic
Remedy and Its Constituent Plant Tinctures Tested Sepa-
rately or in Combination,” Arzneimittelforschung, Vol. 53,
No. 12, 2005, pp. 823-830.