By: Ethan Basch, Steven Gabardi, Catherine Ulbright

Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increase in g-glutamyltransferase and alkaline phosphatase levels in animals, and headaches.

Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powdered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended.

Bitter melon may have hypoglycemic effect, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring
Index terms: Alternative; Antidiabetic agents; Diabetes mellitus; drug interactions; Momordica charantia; Plants; Toxicity.

Bittermelon (Momordica charantia) is used primarily as an alternative therapy for diabetes. A member of the Cucurbitaceae family, the plant grows in tropical areas, including parts of the Amazon Basin, Africa, Asia, the Carribean, and South America. The bitter melon plant is a vine with green leaves and yellow flowers; the fruit itself is oblong and green, resembling a cucumber.

*Bitter melon should be avoided by patients with known allergy or hypersensitivity to bitter melon or members of the Cucurbitaceae (gourd and melon) family, including Persian melon, honeydew, casaba, muskmelon, and cantaloupe.

Adverse effects
No large-scale studies have been undertaken to establish the safety of bitter melon. The most commonly reported adverse effects are discussed here.
Endocrine. Bitter melon has been found to lower blood glucose levelsin animal studied and in several methodological weak human trials.15-18 Proposed mechanisms include insulin-like effects,7,15 stimulation of pancreatic insulin secretion,9 decreased hepatic glucogenesis, increased hepatic glycogen synthesis, and increased peripheral glucose oxidation.8 Two case reports have documented hypoglycemic coma and convulsions in children after administration of a bitter melon tea.19,20

Gastrointestinal. The seeds and outer rind of bitter melon contain a toxic lectin that inhibits protein synthesis in the intestinal wall. However, this has not been correlated with clinical signs or symptoms in humans.13.

Genitourinary. The fertility rate of mice fed with daily bitter melon juice dropped from 90% to 20% in one study.21 Spermatogenesis was inhibited in dogs fed a bitter melon fruit extract for 60 days.22 Studies of MAP30 have not shown an effect on human sperm mortility in vitro.
Hematologic. Individuals with glucose-6-phosphate dehydrogenase deficiency are at risk of developing favism after ingesting bitter melon seeds.20 Favism is defined by the onset of hemolytic anemia and other symptoms, including headache, fever, stomach pain, and coma. The glycosidic compound vicine, a favism-including, chemical, has been isolated from bitter melon.24 Glucose-6-phosphate dehydrogenase deficiency and favism are most common in persons of Mediterranean and Middle Eastern lineage.

Hepatic. Significant increases in g-glutamyltranferase and alkaline phosphatase have been observed in animals after oral administration of bitter melon fruit juice and seed extract.25 These increases have not, however, been associated with significant histopathologic changes in the liver. The clinical relevance in humans has not been studied; caution is warranted, particularly in patients with underlying liver disease,
Neurologic. Headches have been reported after the ingestion of bitter melon seeds,20 but detailed information about headache severity and duration is not available.


Use in pregnancy and lactation
Bitter melon should not be consumed during pregnancy. Two proteins isolated from the raw fruit have demonstrated abortifacient properties in animals.26-28


Drug interactions
Bitter melon may have additive effects when taken concomitantly with other blood glucose-lowering agents. In a poorly described case-series study, additive glucose-lowering effects (measured with GTTs) were seen in eight of nine subjects when bitter melon juice or fried fruit was taken concomitantly with sulfonylureas.16 A 40-year-old woman with type 2 diabetes mellitus experienced additive glucose-lowering effects when ingesting both the sulfonylurea when ingesting both the sulfonylurea chlor-propamide and a curry-containing bitter melon and garlic preparation.29 Garlic has been said to have hypoglycemic properties, although human evidence is limited. In rats, oral bitter melon juice has been found to potentiate the glucose-lowering effects of the sulfonylurea tolbutamide.30


Dosage and administration
Because of the wide variations in preparations techniques, the optimum dosage of bitter melon has not been determined. In the available studies, bitter melon was sometimes administered as a fruit juice doses of 50 mL16 or 100 mL.18 Juice formulations have been reported to have more potent effects on blood sugar and HbAIC levels than the powcer of the sun-dried fruit.17 However, safety and efficacy have not been established for any specific dosage of bitter melon.
Subcutaneous administration of bitter melon has been studied in humans.15 When used subcutaneously, Baldwa et al. used a sliding scale for vegetable insulin isolated from the bitter melon fruit. The safety, efficacy, and optimum dosage for this formulations and route have not been established.
Data on pediatric dosages are lacking. Extreme caution is warranting in view of the two case reports of hypoglycemic coma in children who were given bitter melon tea.19,20


Place in therapy
Bitter melon is used medicinally mainly for the treatment of type 2 diabetes mellitus. Some preliminary evidence suggests that the consumption of bitter melon as whole fruit, extract, or dried powder may reduce blood sugar levels. Most trials have been small, brief, and poorly designed and reported. Since diabetes mellitus is a chronic condition requiring long-term treatment, a longer and better trial is needed to assess safety and clinical efficacy. Such a study could also help in creating a standard dosage form and dosage schedule.
At this point, given the lack of standardization of dosage and administration and the weakness of the efficacy and safety data, routine use of bitter melon cannot be routinely recommended. This alternative medicine agent should be used only under the strict supervision of a licensed health care professional and with careful monitoring of serum blood glucose and possible adverse effects.