February 6, 2014

Nutrient Profile: Bitter melon (Momordica charantia)

Bitter melon has many historical and theoretical uses, ranging from an abortifacient to a hemorrhoid treatment. It also has a long history of use as a hypoglycemic agent. Its hypoglycemic effects have been explored to the greatest extent and have aided in our understanding of its pharmacology and mechanism of action, leading to several studies looking at bitter melon as a hypoglycemic agent in type 1 and type 2 diabetes.

Abstract

Bitter melon has many historical and theoretical uses, ranging from an abortifacient to a hemorrhoid treatment. It also has a long history of use as a hypoglycemic agent. Its hypoglycemic effects have been explored to the greatest extent and have aided in our understanding of its pharmacology and mechanism of action, leading to several studies looking at bitter melon as a hypoglycemic agent in type 1 and type 2 diabetes.
 

Introduction

Most clinicians who use botanical medicine likely have some familiarity with Momordica charantia, or bitter melon, but few of us have ever seen this plant as it is cultivated in the tropics, especially of China, India, East Africa, Central and South America and the Caribbean. Bitter melon, a member of the Cucurbitaceae family, is a perennial climbing vine with long leaves, yellow flowers, and elongated fruit that resembles a gourd or cucumber (it is also referred to as bitter gourd or bitter cucumber). In specialty Asian markets, it is known also as karela.
 
Different parts of the plants are used medicinally (ie, leaves, dried or fresh fruit, vine, whole plant, fresh juice) depending on the condition being treated (eg, high blood pressure, diabetes, diarrhea, fever, skin fungal infections, gastrointestinal cramps, psoriasis, hyperlipidemia, hemorrhoids, glaucoma, infertility). Modern research has not investigated the plant in enough detail to differentiate the effects of each part.
 
Not all of bitter melon’s active constituents have been definitively determined, but we do know that the plant contains alkaloids, glycoside, peptides, acids, cucurbitins, charantin, cucurbitacins, momordine, momorcharins, and proteins.1 It is thought that the primary constituents responsible for the hypoglycemic properties are charantin, insulin-like peptide [plant-(p)-insulin], cucurbutanoids, momordicin, and oleanolic acids.2 The constituents of bitter melon provide a range of pharmacologic effects, including hypoglycemic, antiviral, and antineoplastic activities, but the most compelling area of research is in the field of type 2 diabetes.
 
Bitter melon’s traditional uses in gynecological and female conditions includes: abortifacient, emmenagogue, galactogogue, aphrodisiac, and in the treatment of female infertility. The leaves, vine, and seeds have all been used for these reproductive indications.3
 

Clinical Indications

Diabetes

The ability of bitter melon to decrease serum glucose levels has been investigated in animal studies and in a small number of human studies, which will be discussed below. Reductions in blood sugar after taking bitter melon can be seen quickly—as soon as 30 minutes—with the greatest reduction occurring at 4 hours and lasting for 12 hours.
 
A clinical trial that included 9 type 1 diabetics in the treatment group and 10 type 1 and 2 diabetics in the placebo group found that injections of bitter melon extract, isolated for its crystallized p-insulin, resulted in a statistically significant decrease in blood sugar. The effect was noted 30–60 minutes after subcutaneous injection, a 21.5% drop from baseline glucose, with a peak effect ranging from 4–12 hours with a 28% drop after 12 hours.4 This study was not blinded or randomized, and the placebo group had lower average fasting blood glucose at baseline than did the treatment group, all of which may weaken the validity of the results.
 
A small case series study was published in 1981, in which 9 type 2 diabetics had a baseline glucose tolerance test (GTT) before ingesting 50 mL of bitter melon juice extracted from about 200 g of fresh bitter melon fruit, followed by another GTT. Eight to 11 weeks later, after daily ingestion of 0.23 gm of fried bitter melon, they had another GTT.5 One hour after the intake of the fried fruit, the mean drop in glucose was 6% (not statistically significant). One hour after taking the bitter melon juice, there was a mean drop of 12% in the GTT. The mean glycosylated hemoglobin (HbA1c) also dropped by about 8% from baseline after the 8–11 weeks of fried bitter melon. While the methodology of this study is weak, including lack of controls, the results are important in the effect of bitter melon on type 2 diabetics, for lowering both glucose and HbA1c.
 
Type 2 diabetics were also studied in a case series of 18 patients.6 Each patient was given 100 mL of bitter melon fruit juice 30 minutes before a glucose load and a GTT. Results were compared to each patient’s own previous GTT taken the day before after drinking just water. A statistically significant improvement was seen in 13 of the 18 patients. While each patient served as his or her own control, there was no true control or randomization.
 
Another uncontrolled trial studied a case series of 12 type 2 diabetics over 3 weeks.7 Each individual was given 1 of 2 preparations: 1) a bitter melon aqueous extract of 100 g of chopped boiled bitter melon in 200 mL of water until it was reduced to 100 mL (given once daily); or 2) 5 g of dried fruit powder (given 3 times daily). After the 21 days, those in the powder group had a 25% reduction in mean blood sugar levels. In the aqueous extract group, there was a significant 54% reduction in mean blood sugar levels, and HbA1c dropped from 8.37 to 6.95. These were promising results, although an uncontrolled study in only 12 patients is not compelling.
 
Lastly, more recently and more importantly, a randomized, double-blind, placebo-controlled, trial was done in type 2 diabetics using dried bitter melon fruit and seeds, 3 g/day after meals, for 2 months.8 There was a trend in favor of bitter melon for the reduction of glycosylated hemoglobin, although the study was quite small.
 

Other Potential Uses for Bitter Melon

Several animal studies have shown significant decreases in triglycerides and LDL cholesterol and increases in HDL cholesterol with bitter melon.9–13 In the longest study of 10 weeks, bitter melon extract as given to normal and induced type 1 diabetic rats with elevated total cholesterol, triglycerides and decreased HDL.9 All measurements normalized after the 10 weeks in the mice that received the bitter melon as compared to the non-treated rats.
 
In vitro antiviral activity has been observed with bitter melon seeds and its inhibitory effects on HIV integrating into host cells.14 In vitro research has also demonstrated reduced rates of T lymphocyte infections with HIV-1 and reduced viral replication in infected cells.15,16 Other antimicrobial effects have been observed in vitro as well. Bitter melon extracts have been shown to inhibit the growth of Herpes simplex17 and Epstein Barr virus.18
 
Several animal studies have shown significant decreases in triglycerides and LDL cholesterol and increases in HDL cholesterol with bitter melon.
 
 
There have been some reported antineoplastic effects in vitro,19,20 and bitter melon may potentiate the function of natural killer cells.21,22 A protein isolated from bitter melon extract, MAP30, appears to be the constituent with the antineoplastic activity, and its mechanisms have been attributed to reducing the expression of growth factor receptors. There has been 1 published case report of a patient with gallbladder cancer who consumed bitter melon tea daily and lived 8 years beyond her life expectancy.23 In the case report it was noted that she discontinued the bitter melon tea for several months, during which time the cancer recurred and was the cause of her death.
 
Bitter melon has been shown to have a positive effect on hemorrhoids. A water extract of bitter melon leaves was compared with 4 other herbal therapies in a study of 326 hemorrhoid patients, including some with anal prolapse.24 As a digestive stimulant, it is thought that bitter melon improves digestion, thus resulting in an improvement in hemorrhoids. Bitter melon did not improve anal prolapse in this study. 
 

Dosage

The most appropriate or effective dose of bitter melon is not entirely clear. Powdered, dried fruit has been dosed in a range of 3–15 g/day. The fresh juice has been used at 50–100 mL/day, and an aqueous decoction of the fruit has ranged from 100 to 200 mL per day. Standardized extract dosing ranges from 100 to 200 mg 3 times daily.
 

Adverse effects, cautions, contraindications

Bitter melon has a long history of safe and effective use as a hypoglycemic agent in Asia, Africa, and Latin America. It is considered safe as an oral hypoglycemic agent, but blood glucose monitoring should follow. Bitter melon should be avoided in pregnant women, as it may cause a miscarriage, based on historical use and animal data. Bitter melon seeds contain momorcharin, which have been shown to have antifertility effects in female mice and spermatogenesis inhibition in dogs. A decline of fertility from 90% down to 20% was seen in mice fed daily bitter melon juice.25 Midterm miscarriages were induced in mice who were given isolated momorcharins from bitter melon.26 Also of concern is that bitter melon juice (6mL/kg) caused uterine hemorrhage and death in 2 pregnant rabbits, no uterine hemorrhage in nonpregnant rabbits, and death within 23 days in rabbits continuously fed bitter melon juice.27
 
Bitter melon extract, 1.75 g/day was also given to dogs for 60 days. After 60 days the dogs had no sperm.28 However, in a a laboratory study, the bitter melon constituent MAP30 had no toxic effects on human sperm cells or motility at doses 1,000 times greater than the doses that inhibited HIV-1 and Herpes simplex.29
 
Two case reports in children resulted in hypoglycemic coma after bitter melon tea, and therefore use in children should be avoided until further research is done.
 
Bitter melon may cause allergic reactions in people with allergy or hypersensitivity to members of the Cucurbitaceae family (gourds and melons). While no reports of favism (hemolytic anemia caused by deficiency of glucose-6-phosphate deficiency) have been recorded, bitter melon seeds should likely be avoided by those individuals with glucose-6-phosphate dehydrogenase deficiency because of the vicine or vicine-like compound found in bitter melon seeds. Vicin is a compound that can induce favism.
 
Due to its hypoglycemic effects, bitter melon may have additive effects when taken with other blood glucose-lowering agents. Simple familiar testing and monitoring will ensure safe use of bitter melon preparations. 
 

Summary

Type 2 diabetes mellitus is rapidly becoming a dominant disease not only in the United States, but around the world. The World Health Organization reports that worldwide, the number of people with type 2 diabetes is 240 million; the International Diabetes Foundation reports 285 million—and that’s not counting the more than 400 million with pre-diabetes. It is predicted that each year, an additional 8–10 million will develop the disease. Leading the way are India, China, and the United States.
 
Bitter melon has emerged as one of our strongest botanical interventions for improving blood glucose and HbA1c. The science and native wisdom behind the plant show its value in treating type 2 diabetes mellitus. Combining the use of bitter melon with dietary advice, exercise, lifestyle changes, nutraceuticals, and, if necessary, conventional medicine, can create a comprehensive diabetic treatment strategy. 

Categorized Under

References

  1. Torres W. Momordica charantia Linn. Chemistry and pharmacology. Paper presented at: American Academy of Anti-Aging Medicine; December 2004; Las Vegas, NV.
  2.  Harinantenaina L, Tanaka M, Takaoka S, et al. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull (Tokyo). 2006;54:1017-1021.
  3.  Cunnick J, Takemoto D. Bitter melon. J Naturopath Med. 1993;4(1):16-21.
  4.  Baldwa V, Bhandari C, Pangaria A, Goyal R. Clinical trial in patients with diabetes mellitus of an insulin-like compound obtained from plant sources.Upsala J Med. 1977;82:39-41.
  5.  Leatherdale B, Panesar R, Singh G, et al. Improvement in glucose tolerance due to Momordica charantia (karela). Br Med J (Clin Res Ed). 1981;282(6279):1823-1824.
  6.  Welihinda J, Karunanayake e, Sheriff M, et al. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. J Ethnopharmacol. 1986;17(3):277-282.
  7.  Srivastava Y. Antidiabetic and adaptogenic properties of Momordica charantia extract: an experimental and clinical evaluation. Phytother Res. 1993;7:285-289.
  8.  Dans A, Villarruz M, Jimeno C, et al. The effet of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies.J Clin Epidemiol. 2007;60(6):554-559.
  9.  Chaturvedi P, George S, Milinganyo M, Tripathi Y. Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats. Phytothera Res. 2004;18:954-56.
  10.  Ahmed I, Lakhani M, Gillett M, et al. Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract. 2001;51:155-61.
  11.  Chaturvedi P. Role of Momordica charantia in maintaining the normal levels of lipids and glucose in diabetic rats fed a high - fat and low-carbohydrate diet. Br J Biomed Sci. 2005;62:124-26.
  12.  Chen Q, Li E. Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated with lower tissue triglycride and higher plasma catecholamines. Br J Nutr. 2005;93:747-54.
  13.  Senanayake G, Maruyama M, Sakono M, et al. The effects of bitter melon )Momordica charantia) extracts on serum and liver lipid parameters in hamsters fed cholesterol-free and cholesterol-enriched diets. J Nutr Sci Vitaminol. 2004;50:253-57.
  14.  Wang Y, Neamati N, Jacob J, et al. Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell. 1999;99(4):433-42.
  15.  Lee-Huang S, Huang P, Chen H, et al. Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon. Gene. 1995;161(2):151-56.
  16.  Lee-Huang S, Huang P, Huang P, et al. Inhibition of the integrase of HIV type 1 by anti-HIV plant proteins MAP30 and GAP31. Proc Natl Acad Sci. SUA 1995;92(19):8818-22.
  17.  Bourinbaiar A, Lee-Huang S. The activity of plant-deried antiretroviral protesins MAP30 and GAP31 against Herpes simplex virus in vitro. Biochem Biophys Res Commun. 1996;219:923-29.
  18.  Tropical Plant Database, Raintree Nutrition. Wikipedia, the free encyclopedia. Bitter melon. July 2, 2007.
  19.  Lee-Huang S, Huang P, 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. 2000;20(2A): 653-59.
  20.  Bourinbaiar A, Lee-Huang S. The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against herpes simplex virus in vitro. Biochem Biphys Res Commun. 1996;219(3):923-29.
  21.  Pongnikorn S, Fongmoon D, Kasinrerk W, et al. Effect of bitter melon on level and function of natural killer cells in cervical cancer patients with radiotherapy. J Med Assoc Thai. 2003;86(1):61-8.
  22.  Cunnick J, Sakamoto K, Chapes S, et al. Induction of tumor cytotoxic immune cells using a protein from the bitter melon. Cell Immunol. 1990;126(2):278-89.
  23.  West M, Sidrak G, Street S. The anti-growth properties of extracts from Momordica charantia L. West Indian Med J. 1971;20(1):25-4.
  24.  Olapade E. Clinical evaluation of Rauvolfia vomitoria based extrac tin the treatment of hemorrhoids and anal proloapse in Nigeeria. First world congress on medicinal and aromatic plants for human welfare. Acta Horticulturae. 1993;332:281-85.
  25.  Stepka W, Wilson K, Madge G. Antifertility investigation on Momordica. Lloydia J Nat Prod 1974;37(4):345.
  26.  Chan W, Tam P, Yeung H. The termination of early pregnancy in the mouse by beta-momorcharin. Contraception. 1984;29(1):91-100.
  27.  Sharma V, Sogani R, Arora R. Some observations on hypoglycaemic activity of Momordica charantia.Indian J Med Res. 1960;48(4):471-77.
  28.  Dixit V, Khanna P, Bhargava S. Effects of Momordica charantia L. fruit extract on the testicular function of dog. Planta Med. 1978; 34(3):280-86.
  29.  Schreiber C, Wan L, Sun Y, et al. The antiviral agents, MAP20 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficie3ncy virus type 1. Fertil Steril. 1999;72(4):686-90.