Summary

In addition to their pharmacological or counseling

treatment regimen, 41 diabetes patients took one capsule
containing 500 mg Momordica charantia extract before
two larger meals daily. The literature reports a blood
glucose-lowering effect and action for M. charantia
(bitter melon). After a 6-month observation period, it
was demonstrated in 21/41 patients that their fasting
blood glucose levels, which were as high as 200 mg/dl
before they started taking the bitter melon, dropped by up
to 25% from baseline, and that during this period HbA1c
was lowered by an average of 0.5 percentage points. This
result is consistent with the findings of a UK Prospective
Diabetes Study indicating a risk reduction for the late
sequelae of diabetes by another 10% down to <42%. As
a result, the patients shifted from the group diabetes
mellitus type 2 into the prognostically more favorable
group impaired glucose tolerance (fasting glucose <126
mg/dl). Bitter melon has proven to be a safe balanced
dietary food supplement without any product-specific
side effects.
Diabetes mellitus is increasingly becoming a health
and sociopolitical problem at all age levels, particularly
in countries in the western world, including Arabian
states. All European nations signed the Saint-Vincent
Declaration, which addresses this growing problem.
The agreed aims are to fight this disease along with its
profound social implications (24). Using national and
cross-border disease management programs, healthcare
policies are trying to implement population-related
control and prevention and to improve the care of the
chronically ill. The programs are based on the premise
that risk factors can be eliminated or reduced thereby
lowering the prevalence and morbidity of the disease.
The risk factors can be classified into two groups:

pharmacological therapy options, which are particularly

based on individualized and educational programs
involving nutritional counseling and semi-standardized
exercise regimens.

Ethnopharmacology within the scientific

knowledge process
It is only logical that researching medicine tries to
establish edible and non-toxic plants and herbal
ingredients in the food sector, thereby preventively
counteracting the risk of diabetogenic metabolic
dysfunction or to take curative measures against an
already manifest disease in terms of patient well-being
and laboratory variables. Ethnopharmacology plays an
important role within this scientific knowledge
process. The rational, laboratory-based and targetmolecule-oriented development of compounds,
which, based on their efficacy and toxicity profile, can
be used for early intervention in at-risk populations or
in a person with impaired glucose tolerance, is
extremely time and cost intensive while not providing
any solutions to the problems that arise over the short
term. Thus, it is certainly legitimate to examine the
various ethnomedical systems with regard to their
approaches to fighting the metabolic disease diabetes
mellitus type 2. And, if they prove to be plausible and
feasible, to then test them with regard to their
constituents and efficacy using an adequate and
conventional methodological spectrum provided by
Western medical knowledge.

Bitter Melon Momordica charantia

(I) Obesity, nutrition, limited physical activity, age,

pregnancy and genetic disposition
(II) Hyperinsulinemia, hypoglycemia, dyslipidemia,
and hypertension

The fruits of Momordica charantia L. have been attributed

with just these anti-diabetic effects. The species is a
member of the squash family (Cucurbitaceae) and is
related to the watermelon. Other names are; bitter
gourd, balsam pear (USA), fu kwa (China), karela
(India), ampalaya (Phillipines), Balsambrine
(German-speaking countries). Since the name bitter
melon is very common, we will also use it here.

In the multifactorial analysis, obesity and hyperinsulinemia turned out to be the most powerful predictors
(but also modifiable risk factors) for the development
of diabetes mellitus type 2 with all its afflictions and
socially burdensome late sequelae such as amputation,
dialysis, and blindness. Interventional programs
encompass not only pharmacological but also non-

Bitter melon was originally indigenous to China and

India, but is now also cultivated in South America
(Brazil), USA, Africa, and Europe. M. charantia has
been a well-loved vegetable in Asia for many centuries
and its exceptional health-promoting properties are
highly acknowledged. Now, pumpkin dishes are being
found more and more on European menus.
1

M. charantia is a lanky, green climbing plant with

yellow flowers, their leaves are reminiscent of
grapevine leaves. The warty vegetables look like
cucumbers, the young fruit is green turning to orangeyellow when ripe which then splits. The soft fruit
contains a scarlet red placenta with brown and white
seeds (Fig. 1). It may be confused with M. balsamina
(balsam apple).
Extracts of the fruit are manufactured with both polar
and apolar solvents and tested for their efficacy.

Phytochemistry
As early as in the Forties of the last
century (23) and then again in the
Eighties (11), chemical analysis
were conducted on the constituents
of M. charantia. Alongside the
nutritive, protective constituents
Figure 1
like calcium (20 mg/100 g edible
fruit), carotene (0.13 mg/100 g), riboflavin (0.09
mg/100 g), and vitamin C (88 mg/100 g), it has a high
content of protein (1.6 g/100 g), minerals (0.8 g/100 g),
and carbohydrates (4.2 g/100 g) as well as low fat
content (0.2 g/100 g). A phytosterolin (charantin) (23)
has also been isolated, a mixture of equal parts of
B-sitosterol-B-D-glucoside and a-5, 25-stigmastadein3B-1-ol, reputed to have hypoglycemic effects (21). A
polypeptide with 166 amino acids and a molecular
weight of 11,000 daltons has been isolated from the
fruit and the seeds (P-insulin), which has proved very
homologous with bovine insulin in terms of its amino
acid composition (13), although it is not immunologically
cross-reactive (27).

Phytotoxicology
Ethanolic extracts of the fruit which are administered
either by the oral or subcutaneous route to adult male
gerbils (Meriones hurrianae) in amounts ranging
between 200 and 400 mg/kg of body weight daily for
two weeks reduced spermatogenesis and gonadal
atrophy. Feeding 1.75 g/kg of body weight of M.
charantia fruit to male dogs for 60 days similarly led to
an interruption in spermatogenesis as well as gonadal
atrophy. The prostate conversely was not affected (8,9).
The bitter melon is a very common vegetable in Asia,
and in general, can be regarded as a safe food. When

consumed in excess, however, it can lead to diarrhea

and stomachache. However, the relevant side effect,
while at the same time constituting its physiological
carbohydrate metabolism regulating action, is
frequently described as the property that considerably
reduces blood sugar after ingestion (4, 14). This kind of
efficacy plays a particular role in non-insulin dependent diabetics and determines drug interactions with
oral anti-diabetics (sulfonyl ureas, phenformin/ metformin, thiazolidine) and also insulin. The
concomitant use of M. charantia extracts and the
required blood-sugar lowering therapy may not lead to
hypoglycemia and must therefore take place under
medical supervision.

Pharmacological actions
One working group in Hong Kong discovered two
proteins (a and B-momorcharin) in the seeds of M.
charantia that modulate the activity of T- and B-lymphocytes and suppress the macrophage activity (17)
but are not cytotoxic. Furthermore, a pure protein
(MAP30) was isolated from bitter melon which, on its
own or as recombinant protein (re-MAP30), can
inhibit virus expressions during the various life cycles
of the HIV virus, both during the acute infectious
phase as well as during the replicative phase chronically infected cells. At the same time, anti-tumoral activity has been described for re-MAP30 (16). An 80%
ethanolic extract of bitter melon exhibits both
anti-mutagenic activity in the bacterial (Salmonella)
B-glucuronidase test and chemopreventive action with
regard to colon carcinogenesis in male F344-rats (6).
The preventative action specifically influences the
promotion phase and not the initiation phase. A hot
water extract of bitter melon significantly inhibits the
spontaneous development of breast tumors in
nulliparous SHN mice (20). Various momordins in
bitter melon inhibit the binding of the transcription
factors jun/fos on DNA, which led the authors to
presume that they act cytotoxically on jun/fos
overexpressing cells (15).
In addition to the anti-viral action (5, 10), the anticarcinogenic action of bitter melon has not yet attracted
the full interest of researchers, although the many,
often anecdotic reports about the blood-sugar lowering
action of bitter melon, combined with the positive
reports from clinical trials (1, 14) provide justification
for a field study, where bitter melon extract was given
2

to non-insulin dependent diabetics as a balanced dietary

food supplement to determine whether critical laboratory
parameters (hBA1c, fasting glucose levels) would change
significantly. More recently, and especially in the past six
years, various working groups and authors have focused
increasing attention on the blood sugar-lowering action
of bitter melon.

involved in a drug trial as defined in the terms of the

(German) Drug Law on the licensing of new drugs,
rather that a balanced dietary food supplements was
involved in combination with oral antidiabetics that can
contribute to having a positive effect on carbohydrate
metabolism. Insulin-dependent patients were excluded.
Depending on the physicians diagnosis, all licensed oral
antidiabetics were used.

Rationale
The remarkable evidence gained in the various pharmacological studies on animal species and on humans, but
also the available reports on the clinical relevance (1, 14)
of the properties of bitter melon provides justification for
a field study to determine whether laboratory parameters
such as fasting glucose levels and HbA1c are significantly
changed when a standardized extract is taken. To test the
hypothesis, non-insulin dependent diabetics with WHO
classification of NIDDM type 2 were given the extract as
a balanced dietary food supplement.

Study Design
The study was conducted according to an open-label and
prospective design (protocol and original study data on
file/KSZ) in a general medical practice (G.G.) and a
practice specializing in nephrology (S.H.). Nine male
and 11 female (G.G.) and 10 male and 11 female (S.H.)
patients with an age distribution between 40 and 90 years
that was relevant to the practices were observed in a
controlled setting. The patients were instructed that, in
Asia, America, and now to an increasing extent in
Europe, a vegetable from the squash family has been on
the market, and that the scientific literature reports that
It may be able to lower blood sugar levels. They gave
their written consent to take one capsule containing 500
mg M. charantia extract before each of two of their daily
larger meals. They additionally agreed that the necessary
medical glucose test of the fasting serum levels as well as
the HBA1c measurements conducted five times throughout
the 24 weeks of the daily consumption of the capsules
may be used not only to allow the physician to test the
outcome of therapy, but also be evaluated in anonymized
form for scientific purposes.
The therapy prescribed by the physician (pharmacological)
as well as the doctors recommendations on nutrition
and exercise (non-pharmacological) should not be affected
by the consumption of the capsules or quantitatively
corrected. The patients understood that they were not

The statistical analysis included the patients own

monitoring of the clinical course (comparison of the pair
of baseline values [glucose fasting in the serum and
HbA1c]) before ingestion with the subsequent four pairs
of values, recorded after 6, 12, 18, and 24 weeks during
the period of daily consumption of two bitter melon
extract capsules.

Bitter Melon Extract Capsules

An aqueous bitter melon extract with a minimum content of 10% charantin was derived from pesticide-free
crop from China (cultivated in the Jiang Su territory)
that held a certificate concerning heavy metal and bacterial
burden. After repeated analytical testing of the certified
extract in a German laboratory and its release, ARCOChemie (Herdecke) manufactured capsules containing
500 mg of bitter melon according to Good
Manufacturing Practices (GMP). The capsule size was
conducive to unhindered ingestion. The recommendation
was given [that the patients always take the capsules]
with the amount of drink that they individually required.

Tolerability Results
None of the patients complained to the responsible
physician about any adverse concomitant phenomena
during the supplemental consumption of bitter melon
extract for 24 weeks. The physicians were not able to
ascertain any causal connection between the consumption
of the extract and general well-being or any worsening of
diabetogenic metabolism. The results were reaffirmed
that bitter melon extract is a foodstuff with health
promoting constituents in Europe too and can be regarded
as a good and tolerable food supplement.

Results on efficacy
Regarding the fasting values for blood glucose and the
long-term parameter HbA1c, the patients in the present
study were divided into two groups*:
3

*In patients with well-adjusted diabetes, the values for

fasting glucose range between 80 and 100 mg/dl, those
for HbA1c< 6.5%.
Group A: values fasting < 200 mg/dl glucose in the serum
(25/41) with corresponding HbA1c < 8.0% (29/41):

mean of 120 mg/dl glucose (p< 0.01)(Fig, 5). During

this process, glycosylated HBA1c was significantly
lowered by 0.5 percentage points from 6.8 to 6.3 %
(P<0.01).
Figure 3

Group B: fasting values > 200 mg/dl glucose in the serum

(16/41) with corresponding HbA1c > 8.0% (12/41).
Fig. 2-4 show the ideally typical curves for glucose
reduction in the fasting serum parallel to the reduction
in the HBA1c in two patients from group A (Fig. 2 and
3) and one patient from group B (Fig. 4). The time
concentration curves during the observation period
clearly demonstrate that the bitter melon extract exerts
a glucose lowering, and consequently, an HBA1c
lowering action not only as a supplement to drug
therapy (Fig. 2 and 4) but also in addition to nutritional
and exercise counseling therapy, i.e. according to a
wait and watch strategy. The significant reduction in
the HBA1c levels also provides evidence that the mean
glucose levels must have constantly fallen during the
observation period on 24 weeks, since less substrate
(glucose) must have been available for Amadori products
and the Mallard reaction for fucosylation and thereby
led to an increased production of advanced glucosylation
end products (AGE).

A 57 year-old patient without pharmacological medication, but receiving

medical nutritional counseling. All other parameters are as in Figure 2.
Figure 4

Figure 2

An 80 year-old patient on Euglucon N and adjustment treatment for

insulin (Actraphan). All other parameters are as in Figure 2.

Figure 5

A 62 year-old patient who was treated with Meglucon 850 (3 3 1

Tablets) and took two capsules of bitter melon extract (500mg) before
two larger meals. Week 0 is defined as the time point of entry into the
observation; the subsequent time points are measurements of fasting
glucose levels and HbA1c after 6, 12, 18, and 24 weeks (x-axis). The
left y-axis shows the HbA1c values in %, the right y-axis the glucose
levels in mg/dl.

In 21 patients in group A, the fasting values for glucose

in the serum over 24 weeks of observation were significantly reduced form a mean of 162 mg/dl glucose to a

Array of curves and means of the lowering of fasting glucose levels in the
serum during the 24-week supplemental use of bitter melon extract.

In group B, the pattern with regard to changes in the

main parameters was very heterogeneous: increases
(11/41), consistently stable (6/41) or falling values
(3/41) were observed in this population to an equal
extent. In this group, it was particularly noticeable that
the fluctuations in HBA1c and the fasting glucose
values in the serum frequently drifted apart considerably,
i.e. brief, sequential measurements of blood sugar level
did not adequately reflect long-term changes in
HBA1c. Nevertheless, 9/41 patients in this group
experienced an improvement and/or stability of their
disease when the main parameters were taken into
consideration.
As a result for both groups, it can be concluded that, by
taking a daily supplement of bitter melon extract
before two larger meals, non-insulin-dependent
patients can be reclassified into the group of impaired
glucose tolerance patients (up to 126 mg/dl fasting
glucose) assuming proper patient compliance. This
can be considered a remarkable success for an easy-tohandle, supplemental dietary intervention.

Discussion
In the first European field observation on the safety
and efficiency of an extract of Momordica charantia,
its blood sugar-lowering action could be confirmed in
non-insulin-dependent patients. This was particularly
true when their diabetogenic metabolism was determined
by the limits for the two main parameters: fasting
glucose not greater than 200 mg/dl and HbA1c up to
8.0%. This sort of diabetic subgroup could then be
classified into the prognostically more favorable group
with the status impaired glucose tolerance (= fasting
glucose <126 mg/dl).
The patients were distributed into groups A and B for
reasons of plausibility and can be evaluated as an
important result in terms of a cut-off between the
presumed and expected efficacy. In terms of the reality
of clinical routine, the clientele in a general medical
practice will differ considerably form those in specialized
diabetes practice with respect to compliance and daily
recurrent and necessary understanding as well as their
handling awareness when fighting their disease. From
a sociomedical point of view, type 2 diabetics appear to
cope with their disease with more intensiveness and
self consciousness, and are less resistant to counseling

and therapy when dealing with their physicians

recommendations, diet regimens and treatments. This
type of patient will more likely be found in a specialized
practice than in a general practitioners.
The knowingly accepted heterogeneity of the patient
population which was concentrated in group B can
surely explain the differences in both groups.
Nevertheless, the results are seamlessly consistent with
those obtained in the United Kingdom Prospective
Diabetes Study (UKPDS) (18) where the pharmaceutical
compound metformin lowered HbA1c from 8.0 to
7.4%. This was the equivalent of a risk reduction of
32% for diabetes-associated diseases. In patients treated
with sulfonyl urea or insulin, HbA1c dropped from 7.9
down to 7.0%, i.e. a risk reduction of diabetic
complications of 12%.
By taking 1000 mg of bitter melon extract per day in
addition to their oral antidiabetics, our patients in
group A were able to lower their fasting value by 25%
on average and bring their HbA1c down to 6.3%. This
meant and added reduction in relative risk for the late
sequelae of diabetes by 10 percentage points.

Momordica In The Animal Model

Can the encouraging clinical results achieved with
targeted, balanced dietary food supplement be found
to have a molecular biological rationale in animal
models? One Japanese working group was able to
demonstrate a function-structural relationship with
constituents form M. charantia with respect to their
hypoglycemic activity in rats (18). In these experiments,
momordin 1c, given per os, had no insulin-like or
insulin-releasing effect. Rather, it caused substantial
inhibition of glucose transfer form the stomach into
the small intestine and transport to the brush-border
membrane of the epithelium of the small intestine. In
the model of streptozotocin (STZ)-induced diabetes in
the rat, and English-Arabian working group showed
that an M. charantia fruit juice exerted a relevant
regulatory function on glucose metabolism in experimental diabetes mellitus type 2, supporting the
repair/regeneration of beta-islet cells (3). This research
group had published their results on this effect on the
renewal of beta-cells in STZ diabetic rats back in 1998 (2).
5

Using a KK-Ay mouse model, one group of Japanese

researchers demonstrated that the mechanism of
action of M. charantia, at least in part, is based on a
reduction in insulin resistance in the plasma membrane
of the muscles, since the GLUT4 protein was elevated
in the treated animals (19).
Another working group in Birmingham arrived a
slightly differing opinion. They suggested that the
hypoglycemic action is due to an extra pancreatic effect
that is independent of glucose absorption in the small
intestine (7). Another working group in Bangladesh
concluded from their STZ rat model that the blood
sugar lowering action was attributable to the inhibition
of gluconeogenesis and increased glucose oxidation
(26); a mechanism of action, which could also be
demonstrated by an Indian working group with the
results that their STZ rat model showed increase
glucose utilization in the liver (25).
The experimental data clearly indicated that the
constituents of bitter melon have hypoglycemic activity.
The data strengthen the clinical field observations that
the supplemental intake of a bitter melon extract can
lower main parameters such as HbA1c and fasting
glucose and thereby reduce by up to 42% the relative
risk in this patient population for developing late
sequelae. The authors Platel and Srinivasan recommended
back in 1997 (22) that potentially blood sugar-0lowering
vegetables should be included as food on the daily
menu. Their recommendation has now been compellingly
confirmed on the specified extract of Momordica
charantia in a field observation.
Prof. Kurt S. Zaenker, M.D.
University Witten/ Herdecke
Institute for Immunology
Stockumerstrasse 10
58448 Witten

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