Food as Medicine: Shallot (Allium cepa var. aggregatum, Amaryllidaceae)

HerbalEGram: Volume 14, Issue 2, February 2017 Editor’s Note: Each month, HerbalEGram highlights a conventional 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’s) Dietetic Internship Program, led by ABC Education Coordinator Jenny Perez. We would like to acknowledge Perez, ABC Special Projects Director Gayle Engels, and ABC Chief Science Officer Stefan Gafner, PhD, for their contributions to this project. By Hannah Baumana and Catherine Applegateb a HerbalGram Associate Editor b ABC Dietetics Intern (TSU, 2016) Overview Shallot (Allium cepa var. aggregatum, syn. A. ascalonicum, Amaryllidaceae) is a variety of the common onion (A. cepa).1 Shallots grow natively in the mountains of central Asian countries, including Afghanistan, Tajikistan, Pakistan, and parts of Siberia and China, and they gradually spread throughout Europe as international trade expanded.2 It is an herbaceous plant with alternating foliar leaves that sheath at the base to create the superficial impression that they originate from an above-ground stem.1 Shallot bulbs, which are bunched in groups that resemble large garlic (A. sativum) bulbs, are the portion of the plant commonly used.3 While edible, the above-ground stems and leaves generally are discarded. France, the Netherlands, Great Britain, and the United States are major commercial producers of shallots, and many other countries throughout Southeast Asia and Africa also cultivate and export them.1,2 Phytochemicals and Constituents Of all the onion varieties, shallots contain the highest amount of total flavonols, which have been shown to reduce systemic inflammation and cellular oxidation.4 Many of these bioactive components have been isolated and studied in vitro for their potential protective effects against chronic diseases such as cancer and diabetes.5 One such flavonol is quercetin, which is one of the many phenolic compounds found in many fruits and vegetables that exhibit biological activities.6 Quercetin is reportedly more bioavailable from the dry skin of shallots rather than the flesh, where it is mainly found in the form of quercetin glycosides (quercetin glycosides can be broken down in the body to produce quercetin).7 When metabolized, quercetin forms metabolites that are less biologically potent than quercetin glycosides, but these metabolites still retain some anti-inflammatory properties that have been shown to protect against inflammation-related diseases such as cardiovascular disease (CVD).5 Antioxidants are a group of bioactive compounds that, among other activities, reduce free radical damage to lipids and DNA by reactive oxygen species (ROSs). Antioxidants either accept or donate an electron to stabilize ROS and to reduce their damaging capabilities. Phenolic compounds such as flavonols, carotenoids (fat-soluble pigments that give some plants their orange, yellow, and red colors), ascorbic acid (vitamin C), thiols, and tocopherols (vitamin E) are all examples of antioxidant molecules.8 Flavonols have been widely shown to have potent antioxidant activity in vitro and in vivo. Flavonols have also been extensively studied for their actions on inhibiting the proliferation of cancer cells in vitro. The antioxidant capacity and the anti-proliferative ability of flavonols change depending on how these compounds are metabolized. When tested in liver and colon cell lines designed to mimic human metabolism, the antioxidant activity of the flavonols found in shallots was retained more than the antioxidant activity of the flavonols found in other onion varieties.8 Shallots and other Allium crops have high concentrations of organosulfides, which are sulfur-containing phytonutrients that are metabolized by the enzyme alliinase when the plant tissue is ruptured (e.g., from cooking, chewing, or crushing).9,10 These compounds give Allium plants their recognizable flavor and pungency, with different species differing in flavor and pungency due to variations in the concentrations of types of organosulfides.9 Organosulfides are highly bioavailable in animal models, preserved through metabolism, and can be detected in the blood at dose-dependent concentrations.10 As a result, their antioxidant activity is retained. In humans, their bioavailability is unknown, so further investigation is needed to determine whether biologically active concentrations of organosulfides can be achieved through traditional dietary intake or through pharmacological interventions.10 Finally, isoliquiritigenin is a flavonoid found in high concentration in shallots. Like organosulfides, isoliquiritigenin is highly bioavailable.11 Isoliquiritigenin absorption is dose-dependent and varies depending on tissue type. Historical and Commercial Uses There is little information regarding the historical medicinal uses of shallot, which was originally named Allium ascalonicum after its popularity in the city of Ascalon, Syria, but Allium crops generally were used to treat gastrointestinal issues and tumors and known for their anti-microbial properties.12 The Roman naturalist Pliny the Elder mentioned the shallot as one of six types of onions known to the Greeks in his 77 CE encyclopedia Naturalis Historia.1 By 1554, shallots were grown in Spain, Italy, France, and Germany and Baldassare Pisanelli, a 17th-century doctor in Italy, described the shallot as “a delicious food that stimulates the appetite when it is hot and makes tasty to drink.”4 Cultivation of shallots spread to England from France by 1663, and shallots became a common crop in the United States by 1806.1 Today, shallots are used for culinary purposes: cooked in stews and soups, diced raw in salads or to accompany meats, or pickled.1 Modern Research There are limited data regarding the effect of shallots as a whole food on disease, but specific phytonutrients from shallot have been isolated and studied for their activities and effects on different disease states. Cancer Prevention Plants in the genus Allium, including shallot, have been shown to significantly reduce the risk for gastric cancer in humans. A meta-analysis of epidemiological studies showed that the consumption of 20 grams daily of Allium vegetables (equivalent to the weight of one garlic bulb) reduced the incidence of gastric cancer in individuals when compared to those who consumed lower amounts.13 Similarly, the World Cancer Research Fund (WCRF) in conjunction with the American Institute for Cancer Research (AICR) published a comprehensive report of the existing literature on diet and cancer that found strong evidence to support shallot’s inhibiting effect on cancer cell lines.14 In addition to reducing the risk of gastric cancer, Allium vegetables were also credited with reducing the risk of all cancers.14 However, the WCRF/AICR report recommended a higher dosage of Allium vegetables (100 grams daily) to reduce the risk for gastric and other cancers than that specified by the previously mentioned meta-analysis.13,14 Individual phytonutrients present in shallots have been studied for their capabilities to inhibit the initiation, promotion, and progression of certain types of cancer. Isoliquiritigenin, for example, has been shown to be a potent inhibitor of the metastatic potential of human prostate cancer cells.15 This essentially results in the cell’s ability to “turn off” growth in order to prevent the uncontrolled cell growth and division important for tumor survival. Isoliquiritigenin has also been shown to induce apoptosis (normal, pre-programmed cell death) via mitochondrial-mediated effects.16,17 Similar apoptotic effects were observed when hepatoma, gastric, and melanoma cancer cell lines were treated with isoliquiritigenin.16,17 In addition, treatment with isoliquiritigenin in human lung cancer cells resulted in cell cycle arrest, which inhibited cancer cell growth and proliferation.18 Studies that monitor in vivo effects of isoliquiritigenin are needed to further explore the anti-tumor potential of this compound. Isoliquiritigenin has the potential to act as a safe alternative to commonly used chemotherapies. In a mouse study, renal carcinoma was treated with isoliquiritigenin, which suppressed pulmonary metastases without the leukocytopenia and weight loss associated with administration of the commonly used chemotherapy drug 5-fluorouracil.19 More studies are needed to determine the dosage at which isoliquiritigenin is effective and safe in humans, but this phytochemical may offer a promising alternative to approved chemotherapies that are associated with harmful side effects. Organosulfides also contribute to the antioxidant activity of shallots.10 These compounds have been studied in vitro for their ability to halt cell cycle progression, induce apoptosis, and inhibit angiogenesis of tumor cells.10 Similar effects have been observed in vivo, in which organosulfides have been linked to the inhibition of skin carcinogenesis and prevention of both carcinogen-induced colon cancer and carcinogen-induced esophageal tumors in rats.10 In a clinical trial involving the administration of a high dose of metabolized organosulfides (200 mg per day) over a five-year period, researchers observed a 22% lower incidence of all cancers and a 47.3% lower incidence of gastric cancer in these individuals compared to those who did not receive treatment.10 No adverse effects were observed with this high-dose treatment, highlighting the safety of these compounds. However, further research into the efficacy of these metabolites for cancer chemoprevention is needed. Diabetes Shallot as a whole food has been studied for its hypoglycemic activity. In a mouse study, juiced shallot bulbs was administered orally.20 The blood glucose levels of mice treated with shallot bulb juice were found to be 13.3% lower in the treatment group, compared to an increase of 1.57% in the control group and the end of the 15-day study period. Another animal study compared the glucose-lowering effects of a shallot bulb extract and the commonly prescribed blood glucose-lowering drug, metformin, in rats.21 The reduction of blood glucose observed with shallot bulb extract treatment was similar to that observed with metformin. In addition, treatment with the shallot extract significantly inhibited the metabolism of ingested carbohydrates and increased the cellular absorption of circulating blood glucose. Another animal study compared the antioxidant and hypolipidemic properties of the shallot bulb extract and metformin in diabetic rats.22 In the group treated with the shallot bulb extract, the following increases in phase II antioxidant enzyme activity were observed compared to the control group: superoxide dismutase by 65%, glutathione peroxidase by 43%, and catalase by 55%. Metformin only slightly increased superoxide dismutase activity by 8% when compared to the control group. When comparing lipid profiles, the shallot bulb extract affected only very low-density lipoprotein (VLDL), which was reduced by 24% in comparison to the control group. Treatment with metformin was half as effective, reducing VLDL by only 12%. Anti-Inflammatory A high daily intake of flavonoids from fruits and vegetables is associated with an approximately 50% reduction in mortality from CVD compared to consuming low amounts.8 As quercetin is metabolized by the human body, it retains the ability to function as an anti-inflammatory agent and inhibits the expression of adhesion molecules on the surface of endothelial cells.5 (The presence of adhesion molecules on the surface of endothelial cells can contribute to vascular inflammation and the formation of atherosclerotic lesions.5) By reducing these effects and by reducing the damage caused by oxidative stress, flavonols can act as anti-inflammatory agents to further reduce the risk for inflammatory-related diseases such as certain types of cancer, diabetes, and CVD.23 Antimicrobial Allium plants are well-known for their disease resistance, which has been attributed in part to the antimicrobial activity of saponins present within these plants.24 These same properties have also been applied to human pathogens. Exposure of antibiotic-resistant Mycobacterium tuberculosis to shallot bulb extract resulted in bacterial death.25 Organosulfides have specifically been studied for their anti-fungal properties against several genera of human pathogens including Candida, Cryptococcus, Trichophyton, Epidermophyton, and Microsporum.12 Organosulfides have also been shown to be effective against many bacteria, including Bacillus spp., Enterococcus spp., Escherichia coli, Helicobacter pylori, Salmonella typhimurium, Staphylococcus aureus, and Vibrio cholera. Organosulfides have synergistic effects when combined with antibiotics and broad-spectrum fungicides. Nutrient Profile26 Macronutrient Profile: (Per 1/4 cup chopped shallot [approx. 40 grams]) 29 calories 1 g protein 6.72 g carbohydrate 0 g fat Secondary Metabolites: (Per 1/4 cup chopped shallot [approx. 40 grams]) Good source of: Vitamin B-6: 0.14 mg (7% DV) Manganese: 0.12 mg (6% DV) Vitamin C: 3.2 mg (5.3% DV) Dietary Fiber: 1.3 g (5.2% DV) Also provides: Potassium: 134 mg (3.8% DV) Folate: 14 mcg (3.5% DV) Iron: 0.5 mg (2.8% DV) Phosphorus: 24 mg (2.4% DV) Magnesium: 8 mg (2% DV) Calcium: 15 mg (1.5% DV) Thiamin: 0.02 mg (1.3% DV) Trace amounts: Riboflavin: 0.01 mg (0.6% DV) Niacin: 0.08 mg (0.4% DV) Vitamin K: 0.3 mcg (0.4% DV) Vitamin A: 2 IU (0.04% DV) Vitamin E: 0.02 mg (0.01% DV) DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000-calorie diet. Recipe: Kumquat-Shallot Vinaigrette Courtesy of Catherine Applegate Ingredients: 1/3 cup extra virgin olive oil 1 tablespoon champagne or white wine vinegar 1 tablespoon brown or Dijon mustard 1 tablespoon honey 1 small shallot, minced 5 kumquats Directions: Combine all ingredients except the kumquats in a jar or bowl. Grate the zest from two kumquats into the dressing. Halve and seed all kumquats, leaving the peel intact, and juice them into the dressing. Add the juiced kumquats into the jar or bowl. Mix all ingredients together with a whisk or by putting a lid on the jar and shaking it vigorously. Refrigerate in an airtight container for a few hours before use. Serve dressing over a roasted beet or fresh green salad, or use as a sauce over chicken, pork, or fish. References Peterson J. The Allium species (onions, garlic, leeks, chives, and shallots). Staple Food Domest Plants Anim. 1987;2:249-271. Shallots over the world. Shallot.com. Available at: http://www.shallot.com/shallot-en/facts/shallots-over-the-world.aspx. Accessed January 25, 2017. Goldman IL. Onions and other Allium plants. Encycl Food Cult. 1994;(1963):8-14. Fattorusso EF, Iorizzi MAI, Lanzotti VIL, Taglialatela-Scafati O. Chemical composition of shallot (Allium ascalonicum Hort .). J Agric Food Chem. 2002;50:5686-5690. Lotito SB, Zhang WJ, Yang CS, Crozier A, Frei B. Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic Biol Med. 2011;51:454-463. Bonaccorsi P, Caristi C, Gargiulli C, Leuzzi U. Flavonol glucosides in Allium species: A comparative study by means of HPLC – DAD – ESI-MS – MS. Food Chem. 2008;107:1668-1673. Wiczkowski W, Romaszko J, Bucinski A, et al. Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides. J Nutr. 2008;138:885-888. Yang J, Meyers KJ, Van Der Heide J, Liu RH. Varietal differences in phenolic content and antioxidant and antiproliferative activities of onions. J Agric Food Chem. 2004;52:6787-6793. Vazquez-Prieto MA, Miatello RM. Organosulfur compounds and cardiovascular disease. Mol Aspects Med. 2010;31(6):540-545. Powolny AA, Singh SV. Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett. 2008;269:305-314. Cuendet M, Guo J, Luo Y, et al. Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice. Cancer Prev Res. 2010;3(2):221-233. Lanzotti V, Scala F, Bonanomi G. Compounds from Allium species with cytotoxic and antimicrobial activity. Phytochem Rev. 2014;13:769-791. Zhou Y, Zhuang WEN, Hu WEN, Liu GJ, Wu TAIX, Wu XT. Consumption of large amounts of Allium vegetables reduces risk for gastric cancer in a meta-analysis. Gastroenterology. 2011;141:80-89. World Cancer Research Fund / American Institute for Cancer. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington DC: AICR; 2007. Kwon GT, Cho HJ, Chung WY, Park KK, Moon A, Park JH. Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling. J Nutr Biochem. 2009;20:663-676. Jung JI, Chung E, Seon MR, et al. Isoliquiritigenin (ISL) inhibits ErbB3 signaling in prostate cancer cells. BioFactors. 2006;28:159-168. Jung JI, Lim SS, Choi HJ, et al. Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells. J Nutr Biochem. 2006;17:689-696. Ii T, Satomi Y, Katoh D, et al. Induction of cell cycle arrest and p21 (CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett. 2004;207:27-35. Yamazaki S, Morita T, Endo H, et al. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma. Cancer Lett. 2002;183:23-30. Luangpirom A, Kourchampa W, Junaimuang T, Somsapt P, Sritragool O. Effect of shallot (Allium ascalonicum L.) bulb juice on hypoglycemia and sperm quality in streptozotocin induced diabetic mice. Int J Bioflux Soc. 2013;5(1):49-54. Moradabadi L, Kouhsari SM, Sani MF. Hypoglycemic effects of three medicinal plants in experimental diabetes: Inhibition of rat intestinal α -glucosidase and enhanced pancreatic insulin and cardiac glut-4 mRNAs expression. Iran J Pharm Res. 2013;12(3):387-397. Sani MF, Kouhsari SM, Moradabadi L. Effects of three medicinal plants extracts in experimental diabetes: Antioxidant enzymes activities and plasma lipids profiles in comparison with metformin. Iran J Pharm Res. 2012;11(3):897-903. Murthy NS, Mukherjee S, Ray G, Ray A. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies. J Postgr Med. 2009;55(1):45-55. Teshima Y, Ikeda T, Imada K, et al. Identification and biological activity of antifungal saponins from shallot (Allium cepa L. aggregatum group). J Agric Food Chem. 2013;61(31):7440-7445. Amin M, Segatoleslami S, Hashemzadeh M. Antimycobacterial activity of partial purified extract of Allium ascalonicum. Jundishpar J Microbiol. 2009;2(4):144-147. Basic Report: 11677, Shallots, raw. United States Department of Agriculture Agricultural Research Service. Available at: https://ndb.nal.usda.gov/ndb/foods/show/3314. Accessed January 25, 2017.