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Tuesday, 8 November 2016

Food as Medicine: Bitter Melon (Momordica charantia, Cucurbitaceae)

HerbalEGram: Volume 13, Issue 9, September 2016

Editor’s Note: Each month, HerbalEGram highlights a conventional or traditional food and briefly explores its history, traditional uses, nutritional profile, and modern medicinal research. We also feature a nutritious recipe for an easy-to-prepare dish with each article to encourage readers to experience the extensive benefits of these whole foods. With this series, we hope our readers will gain a new appreciation for the foods they see at the supermarket and frequently include in their diets.
The basic materials for this series were compiled by dietetic interns from Texas State University in San Marcos and the University of Texas at Austin through the American Botanical Council’s (ABC) Dietetic Internship Program, led by ABC Education Coordinator Jenny Perez.

By Hannah Baumana and Brittany Markidesb
a HerbalGram Assistant Editor
b ABC Dietetics Intern (Texas State University, 2015)

History and Traditional Use
Overview

Bitter melon (Momordica charantia, Cucurbitaceae) is a slender-stemmed, warm-climate, herbaceous annual vine. With palmate, deeply lobed leaves, bitter melon has fragrant yellow flowers and produces an elongated fruit that is harvested for food when immature.1 The immature fruit has white or green skin with white flesh, is oblong and pointed at the blossom end, and has a pebbled texture with smooth, lengthwise ridges; it resembles a small, wrinkly cucumber (Cucumis sativus, Cucurbitaceae).2 Chinese varieties of bitter melon bear fruit that are longer and relatively smooth, while Indian varieties bear shorter fruit with a more textured skin.3 As the fruits begin to mature, their bitterness increases and the color gradually turns from green to yellow or orange. At maturity, the fruit splits open, revealing orange flesh and a bright red placenta to which the seeds are attached.2
Bitter melon grows well in wet, tropical areas such as South America, including the Amazon basin, Brazil, and Guyana; the Caribbean; eastern Africa; and Asian countries including India, China, the Philippines, Pakistan, Nepal, and Sri Lanka.4 Domestication of bitter melon began in eastern Asia, most likely in eastern India or southern China.5 Although early archeological evidence for the presence of bitter melon in these regions is sparse, Ayurvedic texts written in Sanskrit from 2000 to 200 BCE mention wild or small-fruited cultivated forms. In China, the earliest written reference to the fruit dates back to 1370 CE.

Phytochemicals and Constituents
The immature bitter melon fruit is a good source of vitamin C and also provides vitamin A, phosphorus, and iron.6 Bitter melon contains other phytochemicals including phenolic compounds and flavonoids, cucurbitane-type triterpenes, and insulin-like peptides.
Triterpenoid compounds called cucurbitanes, which have cancer chemopreventive properties in mice, have been identified in Momordica charantia fruit.7 In vitro tests have shown that these compounds may also inhibit viral infections such as Epstein-Barr, a virus in the herpes family that causes infectious mononucleosis (commonly called “mono”).

Historical and Commercial Uses
Bitter melon is used in traditional medicine practices throughout Asia, Africa, and Central and South America.1,6 Its primary traditional use is the regulation of blood glucose in people with diabetes.4*
Bitter melon has also been traditionally used to relieve gastrointestinal symptoms, to treat colic, to stimulate menstruation, and as an antiviral for measles and hepatitis. In Turkish folk medicine, preparations of bitter melon fruit are used topically to heal wounds and internally to treat peptic ulcers.6 In India, it is used as an antidiabetic, abortifacient, anti-parasitic, laxative, and contraceptive. It is also used as a galactagogue (to increase breastmilk flow) and a purgative, and to treat eczema, malaria, gout, jaundice, abdominal pain, kidney stones, leukorrhea (vaginal discharge), inflamed hemorrhoids, pneumonia, psoriasis, rheumatism, fever, and scabies.
The fruit and seeds are the primary medicinal components of bitter melon; however, some traditional medicine preparations involve the stem and leaves as well.4 The bitter flavor is considered a desirable characteristic for medicinal preparations, and domesticated plants have been selectively bred to produce fruit with a high level of bitterness. Bitter melon dietary supplements are sold in various forms such as powder, juice, and extracts. Supplement capsules generally contain extracts made from the fruit, seed, stem, leaf, or some combination.
Bitter melon is a popular culinary fruit in Asia.1 The unripe fruits of bitter melon are cooked alone or with other vegetables, meat, or fruit. They can be stuffed, stir-fried, or used in small quantities to add bitter flavor to soups and other preparations.5 Often, the fruits are soaked in salt water or parboiled before cooking in order to reduce the bitter taste. The fruits also can be pickled or dehydrated. The fruit, flowers, and young shoots of bitter melon are used as flavoring agents in many Asian dishes. Young shoots and leaves are cooked and eaten as leafy vegetables, and leaves and fruit extracts are used to prepare tea.  The unripe fruit often can be purchased in Asian grocery stores for use in culinary preparations.

Modern Research
The potential health benefits of bitter melon have been investigated in more than 40 animal studies and human clinical trials. Although the body of literature on bitter melon presents some conflicting results, many studies support the traditional use of bitter melon for people with diabetes, as it has been observed in modern research to have anti-diabetic and anti-inflammatory actions, aid in the reduction of body fat and visceral adiposity (intra-abdominal fat), and improve dyslipidemia (abnormal lipid levels) and hypertension associated with the disease.4,6
In animal models, bitter melon supplementation has been shown to have anti-hyperglycemic effects.8-10 Bitter melon is believed to exert glucose-lowering actions through several mechanisms, such as prevention of glucose absorption into the blood, enhancement of glucose uptake by peripheral tissues, and potentiation of insulin.11


Prevention of Glucose Absorption
There are a variety of glucose transporters in the body, which are expressed in different tissues, and facilitate the uptake of glucose into these tissues. In the gastrointestinal tract, one of the glucose transporters is a sodium/potassium ion pump. Bitter melon juice was observed to inhibit this absorption pathway in diabetic rats.12 Bitter melon extract also was demonstrated to inhibit glucose absorption by decreasing the activity of alpha-amylase and alpha-glucosidase, the primary enzymes responsible for digesting carbohydrate chains into smaller carbon chains.13

Enhancement of Glucose Uptake
In individuals with type 2 diabetes mellitus, hyperglycemia is caused, in part, by a decreased ability of glucose transporters to move glucose from systemic circulation into peripheral tissues. Bitter melon has been shown to increase the expression of the primary glucose transporter responsible for transporting glucose into skeletal muscle cells: glucose transporter type 4 (GLUT4).14

Potentiation of Insulin
Insulin, which is synthesized in and released from pancreatic beta-cells, is a vital hormonal regulator of glucose homeostasis. Type 2 diabetes mellitus is characterized by decreased insulin function and/or production, which leads to increased serum glucose levels. Bitter melon was shown to potentiate the actions of insulin by maintaining the structural integrity of pancreatic beta-cells15 and by increasing insulin secretion.16,17

Clinical Trials
Human trials primarily have investigated the potential of bitter melon as an antidiabetic treatment. In humans, bitter melon supplementation has been shown to work synergistically with diabetes medications metformin and glibenclamide,18 decrease incidence of metabolic syndrome and reduce waist circumference,19 and reduce levels of advanced glycation end products (AGEs),20 which are the result of sugar molecules binding to proteins or lipids, a process known as “glycation.” (AGEs play a role in the development of degenerative diseases, including diabetes.) However, few of these trials are randomized, double-blind, and placebo-controlled, and study results from these few trials are conflicting and inconclusive. Therefore, it would be prudent to conduct additional randomized, placebo-controlled studies investigating the use of bitter melon among patients with type 2 diabetes mellitus.

Body Fat and Visceral Adiposity
Bitter melon has been shown to reduce body fat and visceral adiposity in animal studies via the upregulation of key proteins involved in beta-oxidation and mitochondrial respiration (mitochondria are the cellular units that provide energy for each cell in the body). The oxidation of fatty acids allows the body to use fat cells as fuel rather than allowing them to accumulate.
Fatty acid oxidation is carried out in the mitochondria within cells.21 Inhibition of long-chain fatty acid (LCFA) oxidation has been shown to increase fat deposits and insulin resistance in animals on a high fat diet, while increased expression of the enzymes that catalyze fatty acid oxidation has been observed to improve lipid-induced insulin resistance by increasing the mitochondrial fatty acid intake, and therefore the rate of oxidation, and enhancing insulin sensitivity in muscle tissue in rats fed a high fat diet.22 Bitter melon supplementation has been shown to decrease body weight of rats fed a high fat diet by increasing the expression of oxidative enzymes in liver and muscle cells.23

Dyslipidemia
Dyslipidemia is characterized by abnormal levels of triglycerides, low-density lipoproteins (LDL), and low levels of high-density lipoproteins (HDL) in the bloodstream. Dyslipidemia is associated with development of atherosclerosis (hardening of the arteries) and cardiovascular disease.
Bitter melon has been shown to lower total cholesterol, triglycerides, and LDL and increase levels of HDL in rats.24 There are several proposed mechanisms for this action. One of them is the decreased pancreatic lipase activity observed in rats fed a corn oil-heavy diet and treated with the saponin fraction of bitter melon.25 Pancreatic lipase is an important enzyme for fat digestion and absorption. Decreased activity can result in less dietary fat absorbed, which can lead to decreased serum levels of triglycerides. Bitter melon may also lower serum lipid levels by decreasing apoB secretion.26 ApoB is one of the protein components of lipoproteins. Elevated levels of apoB have been correlated with the development of cardiovascular disease.

Hepatoprotective Effects
Bitter melon has been observed to protect and enhance liver function, which has been attributed to its antioxidant capacity to scavenge free radicals.1 Bitter melon supplementation has been shown to normalize levels of total bilirubin and liver enzymes, while increasing levels of antioxidants in rats.27,28 In addition to its antioxidant effects, bitter melon may also protect the liver by reducing fat accumulation and preventing steatosis (fat accumulation in liver cells).29 Supplementation of bitter melon has been shown to downregulate fibroblast growth factor (FGF) 21 levels in livers of mice, which can decrease the risk of developing non-alcoholic fatty liver disease.30

Consumer Considerations
Bitter melon is easily cultivated and commonly eaten as a vegetable throughout the Asian continent and the Pacific Islands region with no serious adverse effects; however, consumption of large quantities of bitter melon can cause diarrhea and gastrointestinal upset.31 Consumption of bitter melon is contraindicated during pregnancy, as bitter melon has been shown to cause uterine hemorrhage in pregnant rats. As the synergistic effects of bitter melon with diabetes medications is still not fully understood, patients who take medication or insulin to manage diabetes should consult their physician before consuming bitter melon.32

* While diabetes is a growing problem in modern times, the first mention of it in the written record occurs in an Egyptian manuscript, the Ebers Papyrus, dated to approximately 1500 BCE.33 The papyrus is a medical text that describes a number of ailments, including a mention of a condition that caused “too great emptying of the urine,” which experts have interpreted as a reference to diabetes. Indian medical literature from the same time period labeled the condition “honey urine” and observed the presence of ants attracted to urine samples. Modern traditional healers in Nigeria still use this diagnostic technique, in addition to observing the patient’s weight, thirst, and urination habits.34 The term “diabetes” was coined by Apollonius of Memphis in 230 BCE from the Greek words dia (“through”) and betes (“to go”).33


Nutrient Profile35
Macronutrient Profile: (Per 1 cup 1/2-inch pieces [approx. 93 g])
87 calories
1 g protein
3.4 g carbohydrate
0.2 g fat
Secondary Metabolites: (Per 1 cup 1/2-inch pieces [approx. 93 g])
Excellent source of:
Vitamin C: 78.1 mg (130.2% DV)
Very good source of:
Folate: 67 mcg (16.8% DV)
Dietary Fiber: 2.6 g (10.4% DV)
Good source of:
Vitamin A: 438 IU (8.8% DV)
Potassium: 275 mg (7.9% DV)
Vitamin K: 4.8 mcg (6% DV)
Also provides:
Magnesium: 16 mg (4% DV)
Manganese: 0.08 mg (4% DV)
Phosphorus: 29 mg (2.9% DV)
Thiamin: 0.04 mg (2.7% DV)
Riboflavin: 0.04 mg (2.4% DV)
Iron: 0.4 mg (2.2% DV)
Vitamin B6: 0.04 mg (2% DV)
Niacin: 0.37 mg (1.9% DV)
Calcium: 18 mg (1.8% DV)
Vitamin E: 0.14 mg (1% DV)
DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000 calorie diet.


Recipe: Bitter Melon Coconut Curry
Recipe courtesy of Brittany Markides
Ingredients:
  • 4 medium bitter melons
  • Kosher salt
  • 1 teaspoon each turmeric and ground cumin
  • 1 tablespoon garam masala spice blend
  • 1 tablespoon vegetable oil
  • 1 medium onion, diced
  • 2 cloves garlic, minced
  • 1 tablespoon fresh ginger, grated
  • 2 jalapeños, stems and seeds removed, chopped finely
  • 4 tomatoes, cored and diced
  • 1 cup coconut milk
  • Juice of 1 lime
  • Cooked rice, for serving
Directions:
  1. Slice the melon in half lengthwise, remove the seeds, then slice in 1/2-inch slices. Combine the turmeric, cumin, and garam masala in a small bowl.
  2. In a large bowl, salt the melon slices liberally and leave the slices to rest for 20 minutes.
  3. While the melon rests, bring a saucepan of water to a boil. Add the rested melon slices and boil for 2 minutes. Both salting and par-boiling help tame the bitterness of the melon.
  4. Remove the bitter melon and pat dry. Sprinkle with spice mixture and toss to coat.
  5. In a medium skillet, heat the oil over medium-high heat until it shimmers. Add the onion and cook 5-10 minutes, or until translucent but not browned. Lower the heat to medium, add the garlic, ginger, and jalapeño, and cook until fragrant.
  6. Add the tomatoes, bitter melon, and coconut milk to the skillet. Bring to a simmer and cook 10-15 minutes, or until flavors have melded together and the liquid has thickened slightly.
  7. Remove from heat and stir in lime juice. Serve over rice.
References
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  2. Meyers C. Specialty and Minor Crops Handbook. 2nd ed. Sacramento, CA: University of California Agriculture & Natural Resources; 1998:22-24.
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  4. Singh J, Cumming E, Manoharan G, Kalasz H, Adeghate E. Medicinal chemistry of the anti-diabetic effects of Momordica charantia: active constituents and modes of actions. Open Med Chem J. 2011;5(Suppl 2):70-77. doi:10.2174/1874104501105010070.
  5. Behera TJ, Behera S, Bharathi LK. Bitter gourd: Botany, horticulture, breeding. Hortic Rev (Am Soc Hortic Sci). 2010;37:101-141.
  6. Grover JK, Yadav SP. Pharmacological actions and potential uses of Momordica charantia: A review. J Ethnopharmacol. 2004;93(1):123-132. doi:10.1016/j.jep.2004.03.035.
  7. Akihisa T, Higo N, Tokuda H, et al. Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects. Journal of Natural Products. 2007;70(8):1233-1239.
  8. Ojewole JAO, Adewole SO, Olayiwola G. Cardiovascular topics hypoglycaemic and hypotensive effects of Momordica charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats. Cardiovascular Journal of South Africa. 2006;17(5):227-232.
  9. Sridhar MG, Vinayagamoorthi R, Arul Suyambunathan V, Bobby Z, Selvaraj N. 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. 2008;99:806-812. doi:10.1017/S000711450783176X.
  10. Chaturvedi P, George S. Momordica charantia maintains normal glucose levels and lipid profiles and prevents oxidative stress in diabetic rats subjected to chronic sucrose load. J Med Food. 2010;13(3):520-527. doi:10.1089/jmf.2009.0151.
  11. Chaturvedi P. Antidiabetic potentials of Momordica charantia: multiple mechanisms behind the effects. J Med Food. 2012;15(2):101-107. doi:10.1089/jmf.2010.0258.
  12. Mahomoodally MF, Fakim AG, Subratty AH. Momordica charantia extracts inhibit uptake of monosaccharide and amino acid across rat everted gut sacs in-vitro. Biol Pharm Bull. 2004;27(2):216-218.
  13. Ahmad Z, Zamhuri KF, Yaacob A, et al. In vitro anti-diabetic activities and chemical analysis of polypeptide-k and oil isolated from seeds of Momordica charantia (bitter gourd). Molecules. 2012;17(8):9631-9640. doi:10.3390/molecules17089631.
  14. 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. 2009;123(1):82-90. doi:10.1016/j.jep.2009.02.039.
  15. Sathishsekar D, Subramanian S. Beneficial effects of Momordica charantia seeds in the treatment of STZ-induced diabetes in experimental rats. Biol Pharm Bull. 2005;28(6):978-983. doi:10.1248/bpb.28.978.
  16. Yibchok-Anun S, Adisakwattana S, Yao CY, Sangvanich P, Roengsumran S, Hsu WH. Slow acting protein extract from fruit pulp of Momordica charantia with insulin secretagogue and insulinomimetic activities. Biol Pharm Bull. 2006;29(6):1126-1131. doi:10.1248/bpb.29.1126.
  17. Keller AC, Ma J, Kavalier A, He K, Brillantes A-MB, Kennelly EJ. Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro. Phytomedicine. 2011;19(1):32-37. doi:10.1016/j.micinf.2011.07.011.
  18. Tongia A, Tongia S, Dave M. Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM). Indian J Physiol Pharmacol. 2004;48(2):241-244.
  19. Tsai C-H, Chen EC-F, Tsay H-S, Huang C. Wild bitter gourd improves metabolic syndrome: a preliminary dietary supplementation trial. Nutr J. 2012;11(1):4. doi:10.1186/1475-2891-11-4.
  20. Trakoon-osot W, Sotanaphun U, Phanachet P, Porasuphatana S, Udomsubpayakul U, Komindr S. Pilot study: Hypoglycemic and antiglycation activities of bitter melon (Momordica charantia L.) in type 2 diabetic patients. J Pharm Res. 2013;6(8):859-864. doi:10.1016/j.jopr.2013.08.007.
  21. Bonnefont J-P, Djouadi F, Prip-Buus C, Gobin S, Munnich A, Bastin J. Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med. 2004;25(5-6):495-520. doi:10.1016/j.mam.2004.06.004.
  22. Bruce CR, Hoy AJ, Turner N, et al. Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes. 2009;58(3):550-558. doi:10.2337/db08-1078.
  23. Chan LLY, Chen Q, Go AGG, Lam EKY, Li ETS. Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. J Nutr. 2005;135(August):2517-2523. doi:135/11/2517.
  24. Chaturvedi P, George S, Milinganyo M, Tripathi YB. Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats. Phyther Res. 2004;18(May):954-956.
  25. Oishi Y, Sakamoto T, Udagawa H, et al. Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction. Biosci Biotechnol Biochem. 2007;71(3):735-740. doi:10.1271/bbb.60570.
  26. Nerurkar P, Lee YK, Motosue M, Adeli K, Nerurkar VR. Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions. Br J Nutr. 2008;100:751-759.
  27. Ching RHH, Yeung LOY, Tse IMY, Sit W, Li ETS. Supplementation of bitter melon to rats fed a high-fructose diet during gestation and lactation ameliorates fructose-induced dyslipidemia and hepatic oxidative stress in male offspring. J Nutr. 2011;141(9):1664-1672. doi:10.3945/jn.111.142299.
  28. Thenmozhi JA, Subramanian P. Antioxidant potential of Momordica charantia in ammonium chloride-induced hyperammonemic rats. Evid Based Complement Alternat Med. 2010;2011(4):1-7. doi:10.1093/ecam/nep227.
  29. Yu Y, Zhang XH, Ebersole B, Ribnicky D, Wang ZQ. Bitter melon extract attenuating hepatic steatosis may be mediated by FGF21 and AMPK/Sirt1 signaling in mice. Sci Rep. 2013;3:3142. doi:10.1038/srep03142.
  30. Morris-Stiff G, Feldstein AE. Fibroblast growth factor 21 as a biomarker for NAFLD: integrating pathobiology into clinical practice. J Hepatol. 2010;53(5):795-796. doi:10.1016/j.jhep.2010.07.003.
  31. Premila MS, Tyler VM. Ayurvedic Herbs: A Clinical Guide to the Healing Plants of Traditional Indian Medicine. New York, NY: Routledge; 2009.
  32. Hudson T. Bitter Melon: A Review of Its Indications, Efficacy, and Safety. Natural Dispensary website. Available at: http://cdn.naturaldispensary.com/downloads/A%20Research%20Review%20of%20Bitter%20Melon.pdf. Accessed September 6, 2016.
  33. Poretsky L. Principles of Diabetes Mellitus. 2nd ed. New York, NY: Springer Science and Business Media; 2010.
  34. Abo KA, Fred-Jaiyesimi AA, Jaiyesimi AEA. Ethnobotanical studies of medicinal plants used in the management of diabetes mellitus in south western Nigeria. J Ethno Pharmacol. 2008;115:67-71.

  35. Basic report: 11024, Balsam-pear (bitter gourd), pods, raw. USDA Agricultural Research Service website. Available at: http://ndb.nal.usda.gov/ndb/foods/show/2832. Accessed August 11, 2016
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