Bitter Melon

Plant Part Used

Fruit

Active Constituents

Sterols (charantin), cucurbitane glycosides (momorcharaside A and momorcharaside B), proteins (momorcharin A and B, MAP-30).(1)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Bitter melon or Karela fruit has long been used in South America and the Orient as not only a food but as febrifuge, abortifacient, emmenagogue, vermifuge, anti-viral, emetic, antihelmintic, and antidiabetic agent among other uses.(1) Recent studies have focused on the beneficial properties of the fruit in blood sugar regulation and hyperinsulinemia, HIV viral infection, and certain cancers. (2),(3),(4),(5)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

200-500mg (standardized extract), 2-3 times daily 1 hour before meals.

Most Common Dosage

200mg (standardized extract), 2 times daily 1 hour before meals.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 5.1% triterpenes or 10% charantin.

Uses

Frequently Reported Uses

  • Blood sugar regulation
  • Insulin resistance/hyperinsulinemia
Other Reported Uses
  • Weight loss support
  • Cholesterol balance
  • Antiviral/Antibacterial

Toxicities & Precautions

General

No toxicity is reported in recommended dosages.

Health Conditions

Do not use in individuals with existing liver disease including alcoholic cirrhosis.(6)

Use with caution in individuals predisposed to cardiac arrhythmias, as bitter melon was reported in a case report to be a contributing factor in atrial fibrillation.(27)

Pregnancy/ Breast Feeding

Based on animal data, do not use in pregnancy due to abortifacient activity.(7) If nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Blood sugar regulation activity

Bitter melon has been reported to significantly improve glucose tolerance in humans and laboratory animals.(4),(8),(9),(28) The currently accepted hypotheses regarding hypoglycemic activity is claimed to be mediated through an insulin secretagogue effect or through an influence on enzymes involved in glucose metabolism.(10) Research indicates that molecules with insulin-like bioactivity may be present in bitter melon seeds.(11) A few studies suggest that the hypoglycemic mechanism of action of bitter melon could be partly attributed to increased glucose utilization in the liver and an insulin secretion effect.(12) More recent laboratory studies have reported that bitter melon seems to up-regulate the mRNA expression level of Glut-4, PPAR gamma and PI3K, with the up-regulation of glucose uptake comparable with insulin and rosiglitazone.(29),(30),(31) A laboratory study reported a significant reduction in fasting blood glucose levels observed in diabetic rats, but no hypoglycemic activity in the treated normal rats.(13)

Diabetes mellitus is associated with an increase in sialic acid concentration along with other complications. A clinical study investigated the use of bitter melon and rosiglitazone (Avandia) in the treatment of NIDDM in 25 patients.(32) Those taking bitter melon reported no significant difference of serum sialic acid and serum glucose concentration as compared to control subjects. However, the concentration of total cholesterol was significantly high in these patients as compared to control subjects but within normal range (160-200mg/dl), suggesting the significant hypoglycemic and lipid-lowering properties of bitter melon. The patients on rosiglitazone treatment showed a significant increase of serum sialic acid concentration along with glucose and total cholesterol concentration as compared to control subjects. The authors concluded that a comparison of serum sialic acid concentration following bitter melon and rosiglitazone treatment revealed no significant difference, but they did concur that the study showed that bitter melon could be more effective in the management of diabetes and its related complications as compared to rosiglitazone.

The effect of bitter melon on fasting and post-prandial serum glucose levels were studied in 100 cases of moderate non-insulin dependent diabetic subjects.(16) Drinking of an aqueous homogenized suspension of the vegetable pulp led to a significant reduction of both fasting and post-prandial serum glucose levels. This hypoglycemic action was observed in 86 (86%) cases. Five cases (5%) showed lowering of fasting serum glucose only. Another interesting study reported on the effects of freeze-dried bitter melon powder on serum glucose level and lipid parameters of the serum and liver were studied in laboratory rats.(17) The bitter melon administration resulted in a consistent decrease in serum glucose levels in rats fed cholesterol-free diets, but not in those fed cholesterol-enriched diets, with no dose-response noted. The authors reported that the bitter melon product had little effect on serum lipid parameters, except for high density lipoprotein (HDL)-cholesterol; however, HDL-cholesterol levels tended to decrease by dietary cholesterol, while they were consistently elevated by dietary bitter melon both in the presence and absence of dietary cholesterol, indicating an antiatherogenic activity of bitter melon. In addition, bitter melon exhibited a marked reduction in the hepatic total cholesterol and triglyceride levels both in the presence and absence of dietary cholesterol, with the reduction of triglyceride levels in the absence of dietary cholesterol being in a dose-dependent manner.

A patented extract of it from Germany called GlucokineÔ contains a highly concentrated and standardized bitter melon concentrate blended with GTF chromium.  A clinical study reported GlucokineÔ reduces fasting glucose and lowers Hemoglobin A1c (HgA1c).  This extract is standardized to contain 10% charantins, an unusually high level of activity compared to most other products on the market.

A small clinical study found that a single, oral dose of bitter melon extract was not effective in glycemic control, energy expenditure or appetite in 5 overweight men.(33) However, it is noted the bitter melon product was freeze-dried fruit and not standardized.

A laboratory animal study found that topical application of a bitter melon extract improved and accelerated the process of wound healing in diabetic animals.(34)

There have been negative reports as to the ability of bitter melon extracts to lower blood sugar levels in laboratory animals.(14),(15)

Antiviral/Antibacterial activity

The mature fruits of bitter melon have been used externally for the rapid healing of wounds and internally for the treatment of peptic ulcers in Turkish folk medicine. A laboratory animal study reported that a potent and dose-dependent inhibitory activity was observed by the administration of ethanol extract of the fruits in peptic ulcer induced by HCL-EtOH and indomethacin in rats.(18) A laboratory study found that bitter melon had effectiveness at improving aminoglycoside activity against methicillin-resistant Staph. aureus.(35)

An anti-HIV plant protein has been identified and purified from bitter melon that is capable of acting against multiple stages of the viral life cycle, on acute infection as well as replication in chronically infected cells.(3),(19) The anti-viral agent from bitter melon is capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in already-infected cells. MAP30 seems to be non-toxic to normal uninfected cells because it is unable to enter healthy cells.(20) In addition to anti-viral action, the protein, termed MAP30, also possesses anti-tumor activity, topological inactivation of viral DNA, inhibition of viral integrase and cell-free ribosome-inactivation activities.(3)

The MAP30 protein has also been reported to be effective against estrogen-dependent human breast cancer MDA-MB-231 in vitro and in vivo, and also a novel antigenic agent against neurofibrillary tangles Alzheimer's disease.(21),(22) Another study indicated that a Thai bitter gourd protein (MRK29), isolated from the ripe fruit and seed of Momordica charantia demonstrated inhibition of HIV-1 reverse transcriptase.(23) A recent laboratory study reported that alpha-momorcharin (alpha-MMC) isolated from bitter melon fruit was found to inhibit HIV-1 III B-inducing syncytia formation and markedly reduced both expression of p24 core antigen and the numbers of HIV antigen positive cells in acutely but not chronically HIV-1-infected culture.(24)

Other activity

A laboratory animal study found that administration of bitter melon extract helped to heal gastric ulceration in rats. The extract showed significant decrease in ulcer index, total acidity, free acidity and pepsin content and an increase in gastric mucosal content, while also reducing the ulcer index in stress induced, ethanol induced and indomethacin induced gastric ulcers and cysteamine induced duodenal ulcer.(36)

Cucurbitane triterpenoids isolated from bitter melon are reported in laboratory studies to have cancer chemopreventative effects.(37) A study completed in rats determined that bitter melon significantly inhibited aberrant crypt focus formation in the colon noting the potential chemoprotective nature of bitter melon against colon carcinogenesis.(25)

Topical application of an extract of bitter melon fruit has been reported to be inhibitory on mouse skin papillomagenesis with the modulatory influence of biotransformation system enzymes.(26)

References

  1. View Abstract: Zhu ZJ, et al. Studies on the active constituents of Momordica charantia L. Yao Hsueh Hsueh Pao. 1990;25(12):898-903.
  2. View Abstract: Khanna P, et al. Hypoglycemic Activity of Polypeptide-P From a Plant Source. J Nat Prod. Nov1981; 44(6):648-55.
  3. View Abstract: Lee-Huang S, et al. Anti-HIV and Anti-Tumor Activities of Recombinant MAP30 From Bitter Melon. Gene. Aug1995;161(2):151-56.
  4. View Abstract: Leatherdale BA, et al. Improvement in Glucose Tolerance Due to Momordica Charantia (Karela). Br Med J. (Clin Res Ed). Jun1981;282(6279):1823-24.
  5. View Abstract: Day C, Cartwright T, Provost J, et al. Hypoglycaemic Effect of Momordica charantia Extracts. Planta Med. Oct1990;56(5):426-9.
  6. View Abstract: Tennekoon KH, et al. Effect of Momordica Charantia on Key Hepatic Enzymes. J Ethnopharmacol. Oct1994;44(2):93-97.
  7. View Abstract: Leung SO, et al. The Immunosuppressive Activities of Two Abortifacient Proteins Isolated From the Seeds of Bitter Melon (Momordica charantia). Immunopharmacology. Jun1987;13(3):159-71.
  8. View Abstract: Sitasawad SL, Shewade Y, Bhonde R. Role of Bittergourd Fruit Juice in Stz-induced Diabetic State In Vivo and In Vitro. J Ethnopharmacol. Nov2000;73(1-2):71-9.
  9. View Abstract: Welihinda J, et al. Effect of Momordica Charantia on the Glucose Tolerance in Maturity Onset Diabetes. J Ethnopharmacol. Sep1986;17(3):277-82.
  10. View Abstract: Platel K, et al. Plant Foods in the Management of Diabetes Mellitus: Vegetables as Potential Hypoglycaemic Agents. Nahrung. Apr1997;41(2):68-74.
  11. View Abstract: Ng TB, et al. Insulin-Like Molecules in Momordica Charantia Seeds. J Ethnopharmacol. Jan1986;15(1):107-17.
  12. View Abstract: Sarkar S, et al. Demonstration of the Hypoglycemic Action of Momordica Charantia in a Validated Animal Model of Diabetes. Pharmacol Res. Jan1996;33(1):1-4.
  13. View Abstract: Rao BK, et al. Antidiabetic and Hypolipidemic Effects of Momordica cymbalaria Hook. Fruit Powder in Alloxan-diabetic Rats. J Ethnopharmacol. Oct1999;67(1):103-09.
  14. Patel K, et al. Effect of Dietary Intake of Freeze Dried Bitter Gourd (Momordica charantia) in Streptozotocin Induced Diabetic Rats. Nahrung. 1995;39(4):262-68.
  15. View Abstract: Ali L, et al. Studies on Hypoglycemic Effects of Fruit Pulp, Seed, and Whole Plant of Momordica charantia on Normal and Diabetic Model Rats. Planta Med. Oct1993;59(5):408-12.
  16. View Abstract: Ahmad N, Hassan MR, Halder H, et al. Effect of Momordica charantia (Karolla) Extracts on Fasting and Postprandial Serum Glucose Levels in NIDDM Patients. Bangladesh Med Res Counc Bull. Apr1999;25(1):11-3.
  17. View Abstract: Jayasooriya AP, Sakono M, Yukizaki C, et al. Effects of Momordica charantia Powder on Serum Glucose Levels and Various Lipid Parameters in Rats Fed With Cholesterol-free and Cholesterol-enriched diets. J Ethnopharmacol. Sep2000;72(1-2):331-6.
  18. View Abstract: Gurbuz I, Akyuz C, Yesilada E, et al. Anti-ulcerogenic Effect of Momordica charantia L. Fruits on Various Ulcer Models in Rats. J Ethnopharmacol. Jul2000;71(1-2):77-82.
  19. View Abstract: Bourinbaiar AS, Lee-Huang S. Potentiation of Anti-HIV Activity of Anti-inflammatory Drugs, Dexamethasone and Indomethacin, by MAP30, the Antiviral Agent from Bitter Melon. Biochem Biophys Res Commun. Mar1995;208(2):779-85.
  20. View Abstract: Lee-Huang S, et al. Inhibition of the Integrase of Human Immunodeficiency Virus (HIV) Type 1 by Anti-HIV Plant Proteins MAP30 and GAP31. Proc Natl Acad Sci. Sep1995;92(19):8818-22.
  21. View Abstract: Liu Z. Microtubule-associated Protein30 (MAP30) and Ubiquitin Detected in Neurofibrillary Tangles of Alzheimer's Disease Brains. Hunan I Ko Ta Hsueh Hsueh Pao. 1998;23(1):11-3.
  22. View Abstract: Lee-Huang S, Huang PL, Sun Y, et al. Inhibition of MDA-MB-231 Human Breast Tumor Xenografts and HER2 Expression by Anti-tumor Agents GAP31 and MAP30. Anticancer Res. Mar2000;20(2A):653-9.
  23. View Abstract: Jiratchariyakul W, Wiwat C, Vongsakul M, Somanabandhu A, Leelamanit W, Fujii I, et al. HIV inhibitor from Thai bitter gourd. Planta Med. Jun2001;67(4):350-3.
  24. View Abstract: Zheng YT, Ben KL, Jin SW. Alpha-momorcharin Inhibits HIV-1 Replication in Acutely But Not Chronically Infected T-lymphocytes. Chung Kuo Yao Li Hsueh Pao. Mar1999;20(3):239-43.
  25. View Abstract: Chiampanichayakul S, Kataoka K, Arimochi H, Thumvijit S, Kuwahara T, Nakayama H, et al. Inhibitory effects of bitter melon (Momordica charantia Linn.) on bacterial mutagenesis and aberrant crypt focus formation in the rat colon. J Med Invest. Feb2001;48(1-2):88-96.
  26. View Abstract: Singh A, et al. Momordica charantia (Bitter Gourd) Peel, Pulp, Seed and Whole Fruit Extract Inhibits Mouse Skin Papillomagenesis. Toxicol Lett. Jan1998;94(1):37-46.
  27. Erden I, Ordu S, Erden EC, Caglar SO. A case of atrial fibrillation due to Momordica charantia (bitter melon). Ann Saudi Med. Jan-Feb 2010;30(1):86-87. No abstract available.
  28. Leung L, Birtwhistle R, Kotecha J, Hannah S, Cuthbertson S. Anti-diabetic and hypoglycaemic effects of Momordica charantia (bitter melon): a mini review. Br J Nutr. Dec 2009;102(12):1703-1708. Epub . Review.
  29. Shih CC, Lin CH, Lin WL, Wu JB. Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats. J Ethnopharmacol. 4 May 2009;123(1):82-90. Epub 2009 Mar 6.
  30. Tan MJ, Ye JM, Turner N, et al. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol. Mar 2008;15(3):263-273. Erratum in: Chem Biol. May 2008;15(5):520.
  31. Kumar R, Balaji S, Uma TS, Sehgal PK. Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPAR gamma and PI3K. J Ethnopharmacol. 10 Dec 2009 ;126(3):533-537. Epub 2009 Sep 8.
  32. Inayat-ur-Rahman, Malik SA, Bashir M, Khan R, Iqbal M. Serum sialic acid changes in non-insulin-dependant diabetes mellitus (NIDDM) patients following bitter melon (Momordica charantia) and rosiglitazone (Avandia) treatment. Phytomedicine. May 2009;16(5):401-405. Epub 2009 Apr 10.
  33. Kasbia GS, Arnason JT, Imbeault P. No effect of acute, single dose oral administration of Momordica charantia Linn.,on glycemia, energy expenditure and appetite: a pilot study in non-diabetic overweight men. J Ethnopharmacol. 29 Oct 2009;126(1):127-133. Epub 2009 Aug 7.
  34. Teoh SL, Latiff AA, Das S. The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin. Clin Exp Dermatol. Oct 2009;34(7):815-822. Epub 2009 Mar 23.
  35. Coutinho HD, Costa JG, Falcão-Silva VS, Siqueira-Júnior JP, Lima EO. Effect of Momordica charantia L. in the resistance to aminoglycosides in methicilin-resistant Staphylococcus aureus. Comp Immunol Microbiol Infect Dis. 2 Sep 2009. [Epub ahead of print]
  36. Alam S, Asad M, Asdaq SM, Prasad VS. Antiulcer activity of methanolic extract of Momordica charantia L. in rats. J Ethnopharmacol. 25 Jun 2009;123(3):464-469. Epub 2009 Mar 26.
  37. Akihisa T, Higo N, Tokuda H, et al. Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects. J Nat Prod. Aug 2007;70(8):1233-1239. Epub 2007 Aug 9.