Bitter Melon

• How It Works

  Bitter melon has been shown to lower blood sugar levels.

  Several active substances in bitter melon have been studied in both animals and humans. They act in the same way as insulin, by increasing the entry of glucose into cells and promoting its processing and storage in the liver, muscle, and fat. Bitter melon also prevents the conversion of stored nutrients to glucose and the release of this glucose into the blood. However, researchers have not established the dosage for lowering high blood glucose levels in diabetes. Therefore it cannot be recommended as a replacement therapy for insulin or hypoglycemic drugs.

  Bitter melon extracts were shown to kill leukemia cells in the laboratory and slow the growth of breast cancer in mice, but it is unknown whether these effects occur in humans. A study in humans showed bitter melon had no effect on the immune system of cervical cancer patients.

• Purported Uses
  • To prevent cancer
    Laboratory studies show that bitter melon extracts can kill certain cancer cells, but it has not been studied in cancer patients.
  • To treat type 2 diabetes
    Small clinical trials show that bitter melon extracts can lower blood glucose levels, but larger and better-designed clinical trials are needed to fully support this use.
  • To reduce fever
    There is no evidence to support this claim.
  • To treat HIV and AIDS
    Preliminary laboratory studies show that bitter melon can slow the ability of HIV to insert its genes into human chromosomes.
  • To treat infections
    Bitter melon extracts can kill certain viruses on contact in the laboratory, but human data are lacking.
  • To relieve menstrual problems
    There is no evidence to support this claim.
• Do Not Take If
  • You are pregnant (Bitter melon can cause vaginal bleeding, premature contractions, and abortion).
  • You are taking insulin (Bitter melon may have additive effects).
  • You are taking hypoglycemic medication for diabetes (Bitter melon may have additive effects).
  • You are taking P-glycoprotein substrates: Bitter melon inhibits P-glycoprotein and can increase the interacellular concentration and toxicity of substrate drugs. Clinical significance is not known.
  • You are taking Cytochrome P450 substrates: Bitter melon extract inhibits CYP2C9 and may affect the metabolism of substrate drugs. Clinical significance has yet to be determined.
• Side Effects
  • Low blood sugar
  • Liver damage (this has been shown in animals, but not in humans)
  • Ingestion of the seeds of bitter melon can cause toxicity to red blood cells, which includes headache, fever, abdominal pain, and coma.
  • A 22-year-old man experienced atrial fibrillation (rapid irregular heartbeat) following ingestion of bitter melon two days before his admission for his dyspeptic complaints. He ingested crushed bitter melon and drank two tablespoons of its juice three times a day, and on the morning of admission as well. His symptoms improved after administering antiarrhythmic medication.
  • A 40-year-old man developed acute gastric ulceration following consumption of half a liter of concentrated homemade liquid extract of bitter melon. His symptoms included severe epigastric pain and hematemesis, which were managed with intravenous fluids, blood transfusion and intravenous rabeprazole.
  • Acute interstitial nephritis due to severe acute kidney injury has been associated with the use of an Ayurvedic formulation (containing bitter melon and other herbs) in a 60-year-old male with diabetes mellitus and hypertension. 
• Scientific Name

  Momordica charantia

• Clinical Summary

  Bitter melon is a perennial plant that grows in the tropical and subtropical regions of Asia, South America, East Africa, and the Caribbean. The edible fruit is used both as food and in medicine to treat diabetes, cancer, viral infections, and immune disorders. Its bitterness is attributed to the presence of alkaloids, momordicosides, and momordicines. In vitro and animal studies indicate anticancer ^{(1) (2) (3)}, antiviral ^{(4) (5) (6)} and lipid lowering ⁽⁷⁾ effects.

  Bitter melon was shown to lower blood sugar levels in both pre-diabetic ⁽³⁹⁾ and diabetic patients ^(8) (40), but robust data are needed to recommend its use ^(9) (40). Studies also indicate that bitter melon extracts have the potential for increasing insulin sensitivity in patients with type-2 diabetes compared to those with type-1 disease ⁽³¹⁾. And supplementation was found useful in reducing pain and improving symptoms in primary knee osteoarthritis patients ⁽⁴¹⁾.

  In a study of cervical cancer patients, bitter melon had no effect on natural killer cell activity ⁽¹⁰⁾.
  Although bitter melon is consumed as food, ingesting the seeds, extracts, and large quantities of juice can cause adverse effects.

• Purported Uses
  • Cancer prevention
  • Diabetes
  • Fever
  • HIV and AIDS
  • Infections
• Mechanism of Action

  In an animal model, bitter melon extract showed hypoglycemic activity by suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase enzymes in the liver ⁽¹⁴⁾. It improved insulin sensitivity, glucose tolerance and insulin signaling ⁽¹⁵⁾; it also reduced insulin resistance by influencing peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma expression ⁽¹⁶⁾ and by modulating the phosphorylation status of insulin receptor and its downstream signaling molecules ⁽¹⁷⁾. The preventive effects of bitter melon against insulin resistance are thought to be via modulation of nuclear factor (NF-kappa B) and phospho-c-Jun N-terminal kinase (JNK) pathways ⁽³⁶⁾.

  Bitter melon may help weight loss by reducing lipogenesis in adipose tissue. Animals that were fed with bitter melon showed lower fatty acid synthase ⁽¹⁸⁾. Bitter melon also affects fat and carbohydrate metabolism by stimulating thyroid hormones and adiponectin, and by enhancing the activity of AMP-activated protein kinase (AMPK) ⁽¹⁹⁾. In another study, it was shown to prevent inflammation and oxidative stress, modulate mitochondrial activity, suppress apoptosis activation, and inhibit lipid accumulation during the development of fatty liver ⁽³²⁾.

  Bitter melon displays cytotoxic activity: A ribosome inhibiting protein (RIP) MCP30 has been shown to inhibit histone deacetylase-1 (HDAC-1) activity and induce apoptosis in prostate cancer cells ⁽¹⁾. In another study, a triterpene extracted from bitter melon activated peroxisome proliferator-activated receptor (PPAR) gamma and induced apoptosis in breast cancer cells ⁽²⁰⁾. Bitter melon juice also caused apoptosis by inducing caspase-3 activation through adenosine monophosphate-activated protein kinase (AMPK) in pancreatic cell lines ⁽³⁾. Similar effects were observed with methanol extracts which increase Bax and decrease the anti-apoptotic protein Bcl-2 ^(21) (22). Other studies demonstrated reduction in metastasis via suppression of MMP-2 and MMP-9 enzymatic activities in lung adenocarcinoma CL1 cells ⁽²³⁾. Bitter melon juice was found effective in decreasing phosphorylation of the protein kinases Akt and ERK1/2, and viability of gemcitabine-resistant pancreatic cancer cells ⁽³⁷⁾. MAP30, a ribosome inhibiting protein (RIP) isolated from bitter melon seeds, inhibited HIV-1 integrase and inactive DNA topology ⁽²⁴⁾, leading to poor viral DNA integration ⁽²⁵⁾ .

• Contraindications

  Bitter melon is contraindicated in pregnant women as it can induce bleeding, contractions, and abortion.

• Adverse Reactions
  • Hypoglycemia and hepatotoxicity were reported in animal studies ⁽²⁷⁾.
  • Toxicity: Ingestion of vicine (seed) may cause favism characterized by headache, fever, abdominal pain, and coma ⁽³⁸⁾.
  • Case Reports
  • A 22-year-old man experienced atrial fibrillation with rapid ventricular response following ingestion of bitter melon two days before his admission for his dyspeptic complaints. He ingested crushed bitter melon and drank two tablespoons of its juice three times a day, and on the morning of admission as well. His symptoms improved after administering antiarrhythmic medication ⁽²⁸⁾.
  • A 40-year-old man developed acute gastric ulceration following consumption of half a liter of concentrated homemade liquid extract of bitter melon. His symptoms included severe epigastric pain and hematemesis, which were managed with intravenous fluids, blood transfusion and intravenous rabeprazole ⁽²⁹⁾.
  • Gastrointestinal problems have been reported with use of bitter melon ⁽¹⁹⁾.
  • Bitter melon may cause a non-allergic type-I like hypersensitivity reaction ⁽³³⁾.
  • Acute interstitial nephritis due to severe acute kidney injury has been associated with the use of an Ayurvedic formulation (containing bitter melon and other herbs) in a 60-year-old male with diabetes mellitus and hypertension ⁽⁴²⁾. 
• Herb-Drug Interactions
  • P-glycoprotein substrates: Bitter melon inhibits P-glycoprotein and can increase the interacellular concentration and toxicity of substrate drugs, including vinblastine and paclitaxel ^(11) (12). Clinical significance has yet to be determined.
  • Cytochrome P450 substrates: Bitter melon extract inhibits CYP2C9 and may affect the metabolism of substrate drugs ⁽³⁰⁾. Clinical significance has yet to be determined.
  • Insulin: Bitter melon may have an additive effect when used concomitantly ⁽⁸⁾.
  • Hypoglycemics: Bitter melon may have additive effects when used concomitantly ^(8) (34).
  • Chemotherapy: Bitter melon extracts may increase bioavailability and efficacy of certain chemo agents, in vitro ⁽³⁵⁾. Clinical significance has yet to be determined.
• References

  1. Xiong SD, Yu K, Liu XH, et al. Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells. International journal of cancer Journal international du cancer. Aug 15 2009;125(4):774-782.

  2. Ray RB, Raychoudhuri A, Steele R, et al. Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer research. Mar 1 2010;70(5):1925-1931.

  3. Kaur M, Deep G, Jain AK, et al. Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells. Carcinogenesis. Jul 2013;34(7):1585-1592.

  4. Lee-Huang S, Huang PL, Chen HC, et al. Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon. Gene. Aug 19 1995;161(2):151-156.

  5. Fan JM, Zhang Q, Xu J, et al. Inhibition on Hepatitis B virus in vitro of recombinant MAP30 from bitter melon. Molecular biology reports. Feb 2009;36(2):381-388.

  6. Waiyaput W, Payungporn S, Issara-Amphorn J, et al. Inhibitory effects of crude extracts from some edible Thai plants against replication of hepatitis B virus and human liver cancer cells. BMC complementary and alternative medicine. 2012;12:246.

  7. Nerurkar PV, Lee YK, Linden EH, et al. Lipid lowering effects of Momordica charantia (Bitter Melon) in HIV-1-protease inhibitor-treated human hepatoma cells, HepG2. Br J Pharmacol. Aug 2006;148(8):1156-1164.

  8. Fuangchan A, Sonthisombat P, Seubnukarn T, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. Journal of ethnopharmacology. Mar 24 2011;134(2):422-428.

  9. Ooi CP, Yassin Z, Hamid TA. Momordica charantia for type 2 diabetes mellitus. The Cochrane database of systematic reviews. 2012;8:CD007845.

  10. Pongnikorn S, Fongmoon D, Kasinrerk W, et al. Effect of bitter melon (Momordica charantia Linn) on level and function of natural killer cells in cervical cancer patients with radiotherapy. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. Jan 2003;86(1):61-68.

  11. Konishi T, Satsu H, Hatsugai Y, et al. Inhibitory effect of a bitter melon extract on the P-glycoprotein activity in intestinal Caco-2 cells. Br J Pharmacol. Oct 2004;143(3):379-387.

  12. Pitchakarn P, Ohnuma S, Pintha K, et al. Kuguacin J isolated from Momordica charantia leaves inhibits P-glycoprotein (ABCB1)-mediated multidrug resistance. The Journal of nutritional biochemistry. Jan 2012;23(1):76-84.

  13. Liu JQ, Chen JC, Wang CF, et al. New cucurbitane triterpenoids and steroidal glycoside from Momordica charantia. Molecules. 2009;14(12):4804-4813.

  14. Shibib BA, Khan LA, Rahman R. Hypoglycaemic activity of Coccinia indica and Momordica charantia in diabetic rats: depression of the hepatic gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-bisphosphatase and elevation of both liver and red-cell shunt enzyme glucose-6-phosphate dehydrogenase. The Biochemical journal. May 15 1993;292 ( Pt 1):267-270.

  15. Sridhar MG, Vinayagamoorthi R, Arul Suyambunathan V, et al. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats. Br J Nutr. Apr 2008;99(4):806-812.

  16. Shih CC, Lin CH, Lin WL. Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet. Diabetes Res Clin Pract. Jun 10 2008.

  17. Nerurkar PV, Lee YK, Motosue M, et al. Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions. Br J Nutr. Mar 5 2008:1-9.

  18. Huang HL, Hong YW, Wong YH, et al. Bitter melon (Momordica charantia L.) inhibits adipocyte hypertrophy and down regulates lipogenic gene expression in adipose tissue of diet-induced obese rats. Br J Nutr. Feb 2008;99(2):230-239.

  19. Saokaew S, Suwankesawong W, Permsuwan U, et al. Safety of herbal products in Thailand: an analysis of reports in the thai health product vigilance center database from 2000 to 2008. Drug safety : an international journal of medical toxicology and drug experience. Apr 1 2011;34(4):339-350.

  20. Weng JR, Bai LY, Chiu CF, et al. Cucurbitane Triterpenoid from Momordica charantia Induces Apoptosis and Autophagy in Breast Cancer Cells, in Part, through Peroxisome Proliferator-Activated Receptor gamma Activation. Evidence-based complementary and alternative medicine : eCAM. 2013;2013:935675.

  21. Li CJ, Tsang SF, Tsai CH, et al. Momordica charantia Extract Induces Apoptosis in Human Cancer Cells through Caspase- and Mitochondria-Dependent Pathways. Evidence-based complementary and alternative medicine : eCAM. 2012;2012:261971.

  22. Fang EF, Zhang CZ, Zhang L, et al. In vitro and in vivo anticarcinogenic effects of RNase MC2, a ribonuclease isolated from dietary bitter gourd, toward human liver cancer cells. The international journal of biochemistry & cell biology. Aug 2012;44(8):1351-1360.

  23. Hsu HY, Lin JH, Li CJ, et al. Antimigratory Effects of the Methanol Extract from Momordica charantia on Human Lung Adenocarcinoma CL1 Cells. Evidence-based complementary and alternative medicine : eCAM. 2012;2012:819632.

  24. Lee-Huang S, Huang PL, Huang PL, et al. Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proceedings of the National Academy of Sciences of the United States of America. Sep 12 1995;92(19):8818-8822.

  25. 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 research. Mar-Apr 2000;20(2A):653-659.

  26. Cunnick J, Takemoto D. Bitter melon (Momordica charantia).  J Naturopath Med.1993;4:16-21

  27. Tennekoon KH, Jeevathayaparan S, Angunawala P, et al.Effect of Momordica charantia on key hepatic enzymes. Journal of ethnopharmacology. Oct 1994;44(2):93-97.

  28. Erden I, Ordu S, Erden EC, et al. A case of atrial fibrillation due to Momordica charantia (bitter melon). Annals of Saudi medicine. Jan-Feb 2010;30(1):86-87.

  29. Nadkarni N, D’Cruz S, Sachdev A. Hematemesis due to bitter melon (Momordica charantia) extract-induced gastric ulcerations. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology. Jan 2010;29(1):37-38.

  30. Appiah-Opong R, Commandeur JN, Axson C, et al. Interactions between cytochromes P450, glutathione S-transferases and Ghanaian medicinal plants. Food Chem Toxicol. Dec 2008;46(12):3598-3603.

  31. Wang HY, Kan WC, Cheng TJ, Yu SH, Chang LH, Chuu JJ.Differential anti-diabetic effects and mechanism of action of charantin-rich extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice. Food Chem Toxicol. 2014 Jul;69:347-56.

  32. Xu J, Cao K, Li Y, et al. Bitter gourd inhibits the development of obesity-associated fatty liver in C57BL/6 mice fed a high-fat diet. J Nutr. 2014 Apr;144(4):475-83.

  33. Sagkan RI. An in vitro study on the risk of non-allergic type-I like hypersensitivity to Momordica charantia. BMC Complement Altern Med. 2013 Oct 26;13:284.

  34. Nivitabishekam SN, Asad M, Prasad VS. Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats. Chem Biol Interact. 2009 Feb 12;177(3):247-53.

  35. Kwatra D, Venugopal A, Standing D, et al. Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance. J Pharm Sci. 2013 Dec;102(12):4444-54.

  36. Yang SJ, Choi JM, Park SE, et al. Preventive effects of bitter melon (Momordica charantia) against insulin resistance and diabetes are associated with the inhibition of NF-κB and JNK pathways in high-fat-fed OLETF rats. J Nutr Biochem. 2015 Mar;26(3):234-40.

  37. Somasagara RR, Deep G, Shrotriya S, Patel M, Agarwal C, Agarwal R. Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells. Int J Oncol. 2015 Apr;46(4):1849-57.

  38. Dutta PK, Chakravarty AK, CHowdhury US, and Pakrashi SC. Vicine, a favism-inducing toxin from Momordica charantia Linn. seeds. Indian J Chem 1981;20B(August):669-671.

  39. Krawinkel MB, Ludwig C, Swai ME, Yang RY, Chun KP, Habicht SD. Bitter gourd reduces elevated fasting plasma glucose levels in an intervention study among prediabetics in Tanzania. J Ethnopharmacol. 2018 Apr 24;216:1-7.

  40. Peter EL, Kasali FM, Deyno S, et al.  Momordica charantia L. lowers elevated glycaemia in type 2 diabetes mellitus patients: Systematic review and meta-analysis. J Ethnopharmacol. 2019 Mar 1;231:311-324.

  41. Soo May L, Sanip Z, Ahmed Shokri A, Abdul Kadir A, Md Lazin MR. The effects of Momordica charantia (bitter melon) supplementation in patients with primary knee osteoarthritis: A single-blinded, randomized controlled trial. Complement Ther Clin Pract. 2018 Aug;32:181-186.

  42. Beniwal P, Gaur N, Singh SK, Raveendran N, Malhotra V. How Harmful Can Herbal Remedies Be? A Case of Severe Acute Tubulointerstitial Nephritis. Indian J Nephrol. 2017 Nov-Dec;27(6):459-461.