Sirn et al

Tropical Journal of Pharmaceutical Research September 2014; 13 (9): 1555-1560

ISSN: 1596-5996 (print); 1596-9827 (electronic)
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.
All rights reserved.

Available online at http://www.tjpr.org

http://dx.doi.org/10.4314/tjpr.v13i9.25
Case Report

A Report of Six Clinical Cases of Lowered Blood

Cholesterol Profile Associated with Supplementation with
Polypeptide K (Diabegard), a Polypeptide Isolated from
the Seeds of Momordica charantia Linn
Yong Yean Sirn1, Lee Cheng Lok1, Zuraini Ahmad2,3 and Muhammad Nazrul
Hakim2,3,4*
1
Well Again Clinic Holistic Healthcare, 46150, Petaling Jaya, 2Department of Biomedical Sciences, Faculty of Medicine and
Health Sciences, Universiti Putra Malaysia, 43400, 3Halal Product Research Institute, Universiti Putra Malaysia, 43400, 4Sports
Academy, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

*For correspondence: Email: nazrul.hakim@gmail.com, nazrulh@upm.edu.my; Fax: +603 8947 1126

Received: 25 March 2014 Revised accepted: 2 April 2014

Abstract
Purpose: To assess six patients with Diabegard supplementation with reference to cholesterol
profiles.
Methods: We report the clinical courses of six individuals taking Diabegard supplementation at 60 and
120 mg/day for 8 weeks.
Results: Patients had a maximum of 52.13 % reduction in low-density lipoprotein (LDL) cholesterol,
47.67 % reduction in triglycerides and 35.78 % reduction in total cholesterol (TC) within 8 weeks of
Diabegard supplementation. Interestingly, high-density lipoprotein (HDL) cholesterol increased by
approximately 23.29 %. Patients also had reduced readings for C-reactive protein (CRP) and
homocysteine (with maximum reduction of 81.58 % and 57.41 % respectively). In some patients, these
parameters were elevated prior to supplementation.
Conclusion: These results suggest that supplementation of Diabegard will improve patients
cholesterol profile by reduction of LDL and TC. Patients also expressed lower CRP and homocysteine
indicating reduced inflammation and reduction of cardiovascular diseases (CVD) risk. However, patients
taking this supplementation are advised to seek medical consultation in monitoring their cholesterol and
other biochemical profile levels.

Keywords: Hypocholesterolemia, Diabegard, Momordica charantia, C-reactive protein, Inflammation,

Cardiovascular disease

Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,
International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African
Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals
(DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts

INTRODUCTION hypercholesterolemia is one of the major

contributing factors for CHD and other CVD.
Approximately 20 % of deaths per year in both Therefore, it is a major worldwide economic and
developing and developed countries are caused medical challenge that most countries are facing
by cardiovascular diseases (CVD) which mainly now [3].
include coronary heart (CHD) disease and stroke
[1]. CHD is considered a world epidemic [2]. One of the treatments for hypercholesterolemia
Elevated blood cholesterol or is using Statins (simvastatin, pravastatin and

Trop J Pharm Res, September 2014; 13(9): 1555

 Sirn et al

atorvastatin) to reduce the body cholesterol of lymphocyte counts and marginally elevated -
biosynthesis that will lead to lower blood levels of glutamyltransferase (GGT). However, her
cholesterol by inhibiting 3-hydroxy-3- cholesterol profile was elevated TC, LDL-
methylglutarylcoenzyme A reductase [4]. Statins cholesterol and HDL-cholesterol (Table 3). Her
are very effective in lowering the low-density CRP level was 7.1 mg/L indicating acute
lipoprotein (LDL) cholesterol by approximately 21 inflammation and elevated homocysteine of 10.7
to 43 % [5]. Unfortunately, statins induce many mol/L. She was advised to take 30 mg Ppk QID
adverse drug reactions. Moreover, patients are at sublingually (8 tablets Diabegard/day) and
risk to more serious ADRs from the long-term practice healthy life-style. After 8 weeks, fasting
ingestion of statins which may include blood analysis revealed a reduction of 24 % TC
and 29 % LDL-cholesterol. Her HDL-cholesterol
mutagenic, teratogenic and carcinogenic effects
level was increased by 21 %. The CRP and
[6].
homocysteine levels reduced by 57 % and 18 %,
respectively. Her elevated of lymphocyte counts
Therefore, about 6080 % of the Worlds also reduced to normal levels.
population now are on herbal plant-based
medicine as their main health care system [7]. Patient 2, a 66-year old Chinese man, also
Momordica charantia Linn (MC) or bitter gourd is diagnosed in early 2012 with type 2 DM. His
the popular plant used for its biomedical blood picture was normal (Table 1) except a low
properties [8]. MC has been extensively used for RBC count. His cholesterol profile was fair with
its blood sugar lowering effects [7]. The only slight elevation of LDL-cholesterol and low
hypoglycemic activity of MC has been reported HDL-cholesterol (Table 3). He was also advised
from its pulps, seeds and leaves [9]. Polypeptide- as patient 1 for his DM condition and after 8
k (Ppk), apolypeptide isolated from seeds of MC, weeks, his HDL-cholesterol increased by
possesses blood glucose level-reducing activity approximately 23 % and LDL-cholesterol
and a small clinical study revealed Ppk not only reduced by 52 % back to optimal level (Table 4).
reduces elevated blood glucose but also
elevated blood cholesterol [10]. We have recently Patient 3 was a 71-year old Malay woman
reported the exact constituents of PpK [11]. Ppk presented with lethargy and her blood analysis is
is sold under the trade name Diabegard (Livvon shown in Table 1. Her blood picture was normal
Marketing, Kuala Lumpur, Malaysia). except a low RBC count. Her cholesterol profile
Diabegard is an over-the-counter dietary was undesirable as her TC, LDL-cholesterol and
supplement used for blood sugar management triglycerides were very high 7.49, 5.24 and 3.65
and overall health. This report describes the mmol/L respectively (Table 3). Her homocysteine
also at the high risk level of 27.1 mol/L. She
outcome of six individuals taking Diabegard
was advised to take 4 tablets of Diabegard
supplementation with reference to cholesterol
daily (60 mg/day Ppk; two tablets BID
profiles.
sublingually). After 8 weeks, her TC reduced by
35 %, LDL-cholesterol by 47 % and triglycerides
EXPERIMENTAL also by 47 %. The homocysteine level reduced to
11.6 mol/L which is a massive 57.41 % to
All patients were presented for their annual borderline levels.
medical examination and a written consent was
taken for this report. Patients were observed by Patient 4 was a 72-year old Indian woman
the physicians from February 2012 till September presented for her biannual medical check-up.Her
2012. All procedures are in accordance with The blood picture was normal (Table 1) but due to her
Declaration of Helsinki [12]. Ethical clearance for slight elevation of glucose (data not shown), She
this study was reviewed and approved by the was advised to take 4 tablets daily of
Faculty of Medicine and Health Sciences Medical Diabegard (60 mg/day Ppk; two tablets BID
Research Ethics Committee, Universiti Putra sublingually). Her cholesterol profile was fair with
Malaysia (Approval no. UPM/FPSK/PADS/T7- borderline levels of TC, LDL-cholesterol and
MJKEtikaPe./F01-158. OKT [03]-72. HDL-cholesterol (Table 3). After 8 weeks, her
cholesterol profile was better with reduction of
Case reports TC and LDL-cholesterol with 12 % HDL-
cholesterol increment.
Patient 1 was a 45-year old Malay woman, who
had been diagnosed with type-2 Diabetes Patient 5, a 68-year old Chinese woman
Mellitus (DM) in 2012. She was in the clinic for presented with complaint of lethargy. Her blood
her normal medical check-up. Her blood picture revealed lowered RBC count, elevated
parameters are presented in Table 1. All leukocytes with increased GGT (Table 1). Her
parameters were normal except slight increment
Trop J Pharm Res, September 2014; 13(9): 1556
 Sirn et al

TC, LDL-cholesterol and triglycerides were slight Patient 6 was a 49-year old Indian man
elevated. The CRP and homocysteine level were diagnosed with type 2 DM. Analysis showed that
also elevated (Table 3). She was also advised to all blood parameters were within normal range
take 4 tablets of Diabegard daily (60 mg/day (Table 1) except his liver function enzymes which
Ppk; two tablets BID sublingually). After 8 weeks, were mildly elevated (Table 1). His cholesterol
the TC was reduced by 9 %, LDL-cholesterol by profile was also slightly elevated with elevation of
13 % and triglycerides reduced by 35 % (Table TC, LDL-cholesterol and triglycerides. He was
3). Interestingly, her HDL-cholesterol increased given Diabegard as for patient 1. After 8 weeks
by 9 % and CRP dropped by a massive 81%. of supplementation, his liver function was back to
The homocysteine also reduced by 49 %. normal (Table2). Table 4 expresses his lowered
cholesterol level.

Table 1: Selected biochemical parameters of patients prior to Diabegard supplementation

Parameter Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient Reference

6 range*
Red blood cell 4.7 2.3 3.2 4.0 3.6 5.35 M:4.5-6.5
(mil/cmm) F:3.8-5.8

White Blood Cell 9.7 7.2 7.1 5.4 6.8 11.0 4.0-11.0
(tho/cmm)

Neutrophils (%) 40.0 75.0 64.0 47.0 76.0 60.0 40-75

Lymphocytes 54.0 20.0 26.0 45.0 18.0 34.0 20-45

(%)

Monocytes(%) 5.7 4.0 6.0 6.0 4.0 5.0 2-10

Eosinophils(%) 0.3 1.0 4.0 2.0 2.0 1.0 1-6

Basophils(%) 0 0 0 0 0 0 0-1

AST (U/L) 32.0 17.0 29.0 25.0 39.0 45.0 <40.0

ALT (U/L) 31.0 17.0 16.0 14.0 21.0 55.0 <50.0

GGT (U/L) 65.0 18.0 12.0 14.0 255.0 68.0 <50.0

ALP (U/L) 78.0 84.0 44.0 91.0 46.0 67.0 M:<125

F:<115

Total protein 82.0 56.0 68.0 68.0 75.0 76.0 62-82

(g/L)

Total bilirubin 10.3 5.1 10.3 10.2 17.8 16.1 <25.7

(mol/L)

*Source: Ref [17]

Table 2: Selected biochemical parameters of patients 12 weeks after Diabegard supplementation

Parameter Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Reference

range*
Red blood cell 4.0 2.0 3.0 4.5 3.5 5.3 M:4.5-6.5
(mil/cmm) F:3.8-5.8

White blood Cell 9.9 6.3 6.9 8.5 6.9 9.7 4.0-11.0
(tho/cmm)

Neutrophils (%) 45.0 74.0 69.0 75.0 75.0 62 40-75

Lymphocytes
(%) 42.0 18.0 23.0 20.0 19.0 27 20-45

Trop J Pharm Res, September 2014; 13(9): 1557

 Sirn et al

Monocytes (%)
10.0 4.0 5.0 4.0 4.0 7 2-10
Eosinophils (%)
3.0 4.0 3.0 1.0 2.0 3 1-6
Basophils (%)
0 0 0 0 0 1 0-1
AST (U/L)
17.0 23.0 18.0 27.0 33.0 39.0 <40.0
ALT (U/L)
19.0 15.0 9.0 19.0 16.0 29.0 <50.0
GGT (U/L)
35.0 14.0 9.0 18.0 88.0 47.0 <50.0
ALP (U/L)
49.0 61.0 52.0 58.0 40.0 62.0 M:<125
F:<115
Total protein
(g/L) 73.0 54.0 73.0 75.0 77.0 76.0 62-82

Total bilirubin 5.6 5.6 9.1 12.5 17.9 14.7 <25.7

(mol/L)

*Source: Ref [17]

Table 3: Lipid profile and cardiovascular risk of patients prior to Diabegard supplementation

Parameter Patient Patient Patient Patient Patient Patient 6 Reference

1 2 3 4 5 range*
Total cholesterol 6.54 4.49 7.49 5.59 6.60 7.20 Desirable:<5.17
(mmol/L) High:>6.20

HDL-cholesterol 1.64 0.73 1.18 1.41 1.37 1.51 Low:<1.04

(mmol/L) High:>1.55

LDL-cholesterol 4.27 3.76 5.24 3.78 4.32 4.95 Optimal:<2.58

(mmol/L) High:4.14

Triglycerides(mmol/L) 1.36 2.12 3.65 0.88 2.50 3.23 Normal:<1.69

High:>2.25
Total/HDL-cholesterol
ratio 4.0 6.2 6.3 4.0 4.8 4.8 Optimal:<3.5
(Index) High:>5.0

C-reactive protein 7.1 ND 3.0 ND 11.4 19.4 Risk-Low:<1.0

(mg/L) High:>3.0
Acute
Inflam:>5.0

Homocysteine 10.7 ND 27.1 ND 36.4 ND Low risk:<10

(mol/L) High:>15

*Source: Ref [17]

Table 4: Lipid profile and cardiovascular risk of patients 12 weeks after Diabegard supplementation

Parameter Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient Reference

6 range*
Total 4.96 4.4 4.81 4.96 5.99 6.74 Desirable:<5.17
cholesterol (-24.16) (-2.00) (-35.78) (-11.27) (-9.24) (-6.39) High:>6.20
(mmol/L)

HDL-cholesterol 1.99 0.90 1.18 1.58 1.50 1.22 Low:<1.04

(mmol/L) (+21.34) (+23.29) (0) (+12.06) (+9.49) (-23.77) High:>1.55

LDL-cholesterol
(mmol/L) 3.03 1.80 2.75 2.93 3.75 4.74 Optimal:<2.58
(-29.04) (-52.13) (-47.52) (-22.49) (-13.19) (-4.24) High:4.14
Trop J Pharm Res, September 2014; 13(9): 1558
 Sirn et al

Triglycerides
(mmol/L)
2.26 1.90 1.91 0.97 1.62 3.63 Normal:<1.69
Total/HDL- (+66.17) (-10.34) (-47.67) (+10.23) (-35.2) (+12.39) High:>2.25
cholesterol
Ratio 5.0 4.9 4.1 3.1 3.99 5.5 Optimal:<3.5
(Index) High:>5.0

C-reactive Risk-Low:<1.0
protein (mg/L) High:>3.0
3.0 ND ND ND 2.1 ND Acute
(-57.75) (-81.58) Inflam:>5.0
Homocysteine
(mol/L) Low risk:<10
8.7 ND 11.6 ND 18.5 ND High:>15
(-18.69) (-57.41) (-49.18)
*Source: Ref [17]

DISCUSSION These events initiated the interest for herbal

cholesterol-lowering therapy [23,24].. Results
Abnormal levels of blood cholesterol, i.e. high from this short report show the possible benefits
LDL-cholesterol and low HDL-cholesterol are of herbal based supplementation in reducing and
strongly associated with CVD because these controlling hypercholesterolemia clinically.
conditions favour atheroma development and
may lead to myocardial infarction, stroke, and/or Oxidative stress, in this case,
peripheral vascular disease [13,14]. This report hypercholesterolemia may initiate and further
describes the cholesterol profile changes in 6 progression of atherosclerosis by stimulating
patients on Diabegard supplementation for 8 inflammation and promoting cytokine production
weeks. The results suggest that Diabegard [25]. Ppk has been proven to be a potent anti-
supplementation improves the cholesterol profile oxidant and this maybe the mechanism of the
of an individual without any drug therapy. reduction of CRP and homocysteine observed in
the patients [11]. Other than drugs and
All 6 patients showed reduction in TC and LDL- supplementations, diet also plays an important
cholesterol from 2 % to as high as 52.13 % role in the maintenance of optimal cardiovascular
(Table 3) in just 8 weeks. Their total/HDL- health [26]. Physical activity is also useful in
cholesterol ratio, a predictor for CHD [15] reducing bad cholesterol, improve cholesterol
improved from 6.3 prior to supplementation to 3.1 profile and reducing risk of CVD [27].
post-supplementation. Indeed, these parameters
suggest that generally patients will have healthier CONCLUSION
cholesterol profile after Diabegard
supplementation. Three of the patients were The results from this report strongly suggest that
having elevated CRP and homocysteine levels. Diabegard supplementation improve the
CRP level rises when there are inflammatory patients cholesterol profile. However, all patients
processes occurring in the body [16]. were advised to continue the supplementation
Hypercholesterolemia will induce intravascular and regular health check-ups. Indeed, further
inflammation and susceptibility to
studies are needed to elucidate the exact
artherosclerosis [13]. CRP dropped to the
mechanism for the cholesterol-lowering
maximum by 81.58 % in Patient 5 suggesting
properties of Ppk. Ppk is not only a supplement
healthier cholesterol profile and reduction of
inflammation. These also followed by the for glucose management [10] but also a potent
reduction of homocysteine, which is a predictor supplement for cholesterol management.
of CVD [17].
REFERENCES
Commercial synthetic hypercholesterol drugs
such as statins are effective in lowering the blood 1. Thomas S, Rich MW. Epidemiolgy, pathophysiology, and
cholesterol level. However, numerous clinical prognosis of heart failure in the elderly. Clin Geriatr
cases have been published reporting the various Med. 2007; 23: 1-10.
ADR induced by statins [18,19]. These ADRs 2. Cordero Fort A, Moreno Arribas J, Martin Arnau A,
include liver damage, myopathy and Nasarre Lorite E, Alegria Barrer E, Alegria Ezquerra
rhabdomyolysis, myalgias and polyneuropathy E. [Prevalence of metabolic syndrome and
[20]. Synthetic drugs may induce more ADRs association with ischemic heart disease in
[21] when compared to herbal remedies [22].

Trop J Pharm Res, September 2014; 13(9): 1559

 Sirn et al

cardiological outpatients]. Rev Clin Esp. 2006; 16. Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S.
206(6): 259-265. "Adipokines: molecular links between obesity and
3. Olshansky SJ, Passaro DJ, Hershow RC. A potential atheroslcerosis". Am. J. Physiol. Heart Circ. Physiol.
decline in life expectancy in the United States in the 2005; 288 (5): H203141.
21st century. N. Engl. J. Med. 2005; 352: 1138-1145. 17. Porter RS, Kaplan JL. The Merck Manual of Diagnosis
4. Sirtori CR, Fumagalli R. LDL-cholesterol lowering or and Therapy.Nineteenth Edition.2011. The Merck
HDL-cholesterol raising for cardiovascular prevention. Publishing Group. Whitehouse Station, N.J., U.S.A.
A lesson from Cholesterol turnover studies and 18. Russo MW, Scobey M, Bonkovsky HL. Drug-induced liver
others.Atherosclerosis. 2006; 186(1): 1-11. injury associated with statins. Review. Semin Liver
5. Jacobson TA. Statin safety: lessons from new drug Dis 2009; 29(4): 412422.
applications for marketed statins. Am J Cardiol. 2006; 19. Bjrnsson E, Jacobsen EI, Kalaitzakis E. Hepatotoxicity
97(8A): 44C-51C. associated with statins: Reports of idiosyncratic liver
6. Clark LT. Treating dyslipidemia with statins: the risk- injury post-marketing. J Hepatol. 2012; 56: 374380
benefit profile. Am Heart J.2003; 145(3): 387-396. 20. Golomb BA, Evans MA. "Statin Adverse Effects: A
7. Lee CL, Yong YS, Zuraini A, Yaacob A, Nazrul Hakim M. Review of the Literature and Evidence for a
Effects of polypeptide-k supplemented soft bun on Mitochondrial Mechanism". Am J Cardiovasc Drugs.
blood glucose level in healthy adults. Int J Nut 2008; 8(6): 373418
Metabol 2011; 3: 710. 21. Somchit N, Sanat F, Gan EH, Shahrin IAW, Zuraini A.
8. Ali L, Khan AKA, Mamun MIR, Mosihuzzaman M, Liver injury induced by the non-steroidal anti-
NaharN,Nur-e-Alam M, Rokeya B. Studies on the inflammatory drug mefenamic acid. Singapore Med J.
hypoglycaemic effects of fruit pulp, Seed and whole 2004; 45(11): 530-532.
plant of Momordica charantia on normal and diabetic 22. Somchit MN, Reezal I, Nur IE, Mutalib AR. In vitro
model rats. Planta Med. 1993; 59: 408412. antimicrobial activity of ethanol and water extracts of
9. Xiang L, Huang X, Chen L, Rao P, Ke L. The reparative Cassia alata. J Ethnopharmacol. 2003; 84(1): 1-4.
effects of Momordica charantia Linn.extract on HIT- 23. Zuraini A, Aziah MRR, Arifah AK, Sulaiman MR, Somchit
T15 pancreatic -Cells. Asia Pac. J. Clin.Nutr. 2007; MN. Aqueous extracts of Andographispaniculata
16: 249252. improve lipid profiles of rats fed with high cholesterol
10. Kanna P. Protein/polypeptide-k obtained from Momordica diet. Int J Pharmacol. 2006; 2(1): 45-49.
charantia. U.S. Patent 6, 831, 162, 2004. 24. Ang K-P, Tan H-K, Selvaraja M, Kadir AA, Somchit MN,
11. Ahmad Z, Zamhuri KF, Yaacob A, Siong CH, Selvarajah Akim AM, Zakaria ZA, Ahmad Z. Cryptotanshinone
M, Ismail A, Hakim MN. In Vitro Anti-diabetic attenuates in vitro oxLDL-induced pre-lesional
Activities and Chemical Analysis of Polypeptide-k and atherosclerotic events. Planta Medica. 2011; 77(16):
Oil Isolated from Seeds of Momordica charantia 1782-1787.
(Bitter Gourd).Molecules 2012; 17(8): 9631-9640. 25. Fernndez-Robredo P, Rodriguez JA, Sdaba LM,
12. Bell DS. Ethics in Diabetic Clinical Trials. Diabetes Care Recalde S, Garca-Layana A. Egg Yolk improves lipid
2001; 24(3): 606-626 profile, lipid peroxidation and retinal abnormalities in
13. Libby P, Ridker PM, Maseri A, Inflammation and a murine model of genetic hypercholesterolemia. J.
Atherosclerosis. Circulation. 2002; 105: 1135-1143. Nutr. Biochem. 2008; 19: 40-48.
14. Hakim NA, Hafizan MT, Baizurah MH, Zainal AA. Serum 26. Dauchet L, Amouyel P, Dallongeville J. Fruits, vegetables
lipoprotein(a) levels in patients with atherosclerotic and coronary heart disease. Nat. Rev. Cardiol. 2009;
peripheral vascular disease in Hospital Kuala 6: 599-608.
Lumpur. Asian J Surgery. 2008; 31(1): 11-15. 27. Esmaelzadeh MR, Soh KG, Abdullah MNH, Bahaman A.
15. Wang TD, Chen WJ, Chien KL, Seh-Yi Su SS, Hsu HC, The effects of combined training on interluken-6 and
Chen MF, Liau CS, Lee YT. Efficacy of cholesterol c reactive protein as non-traditional cardio risk factors
levels and ratios in predicting future coronary heart in inactive students. Pertanika J Social Science
disease in a Chinese population. Am J Cardiol. 2001; Humanities. 2012; 20: 117-128.
88(7): 737-43.

Trop J Pharm Res, September 2014; 13(9): 1560