Food as Medicine: Grapes

HerbalEGram: Volume 12, Issue 12, December 2015 (Vitis vinifera, Vitaceae) 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 Mindy Greenb a HerbalGram Assistant Editor b ABC Dietetics Intern (UT, 2014) History and Traditional Use Range and Habitat Vitis vinifera means “the vine that bears wine” and belongs to the Vitaceae family. Grapes are perennial climbers that have coiled tendrils and large leaves. They contain clusters of flowers that mature to produce small, round, and juicy berries that can be either green (“white”) or red.1 There are seed and seedless varieties, although the seeds are edible and packed with nutrition. The juice, pulp, skin, and seed of the grape can be used for various preparations.2 Grapes are a vine and must be trained to grow along a fence, wall, or arbor.3 The fruit does not ripen after harvesting; therefore, it is important to harvest well-colored and plump berries that are wrinkle-free and still firmly attached to the vine. They are best stored in the refrigerator since freezing will decrease their flavor.1,4 Pesticide use is common in vineyards, and careful washing is recommended when purchasing conventionally grown grapes. As one of the leading commercial fruit crops in the world in terms of tons produced, grapes are cultivated all over the world in temperate regions. The top producers are Italy, France, Spain, the United States, Mexico, and Chile.1,5 Annually, worldwide grape production reaches an average of 60 million metric tons, 5.2 million of which are grown in the United States. Phytochemicals and Constituents Antioxidants are enzymes and nutrients that prevent oxidation, meaning they neutralize highly reactive ions or molecules known as free radicals in the human body by donating electrons, or modulating enzymes that metabolize free radicals. Free radicals are produced naturally through metabolism as part of normal physiological functions (e.g., a defense mechanism against pathogens), but may be produced in excess, creating a situation where they adversely alter lipids, proteins, and DNA, and trigger a number of human diseases. Grape and grape products are good sources of beneficial antioxidant compounds. Grapes contain phytochemicals called polyphenols. Polyphenols are the most abundant source of dietary antioxidants and are associated with numerous health benefits.2,6 The phenolic compounds are more concentrated in the skin of the berry, rather than in the flesh or seeds, and the content tends to increase as the fruit ripens. Grapes contain polyphenols from the classes of flavonoids, stilbenes, and phenolic acids. Red wine and grapes are rich in flavonoids such as anthocyanins and catechins, stilbenes such as resveratrol, and phenolic acids such as caffeic acid and coumaric acid. Red grapes have higher concentrations of these phenolic compounds than red wine grapes. Different grape varietals contain varying amounts of phenolic compounds. Anthocyanins are flavonoids that naturally occur in the plant kingdom and give many plants their red, purple, or blue pigmentation. Vitis vinifera may contain up to 17 anthocyanin pigments, which are contained in the skins.2,7 Grapes also contain other flavonoids, including catechins, epicatechins, and proanthocyanidins. Attempts to study the benefits of individual phytochemicals in humans has been difficult since these phytochemicals are complex and often interact with one another to increase their overall benefits. There are numerous studies using animal models in phytochemical research.8 Animal models have shown that anthocyanins protect against oxidative stress, which can be the beginning stages of many chronic conditions, such as cardiovascular disease, diabetes, and cancer. Grape seeds are a particularly rich source of proanthocyanidins, a class of nutrients belonging to the flavonoid family. Proanthocyanidins, also known as condensed tannins, are polymers (naturally occurring large molecules) with flavan-3-ol monomers as building blocks. The term oligomeric proanthocyanidin (OPC), which also is commonly used to describe these compounds, is not well-defined and is debated among various members of the scientific community. Grape seed extract is available as a nutritional supplement. Partially purified proanthocyanidins have been used in phytomedicinal preparations in Europe for their purported activity in decreasing the fragility and permeability of the blood vessels outside the heart and brain.9 Grapes have a high stilbene, specifically resveratrol, content. Resveratrol, which is found in the skin and seeds of red grapes as well as in red wine, is produced as the plant’s defense mechanism against environmental stressors.1,2,10,11 Resveratrol first gained attention as a possible explanation for the “French Paradox” — the observation that French people tend to have a low incidence of heart disease despite having a typically high-fat diet.1 The antioxidant activity of grapes is strongly correlated with the amount of resveratrol found in the grape.10 Studies have found resveratrol to be anti-carcinogenic, anti-inflammatory, and cardio-protective in animal models.11 However, in a human study in which healthy adults consumed resveratrol, it was determined that the compound was readily absorbed, but it metabolized quickly, leaving only trace amounts.12 In addition to their high resveratrol content, grapes are also an excellent source of vitamin K and provide moderate amounts of potassium, vitamin C, and B vitamins. Historical and Commercial Uses Grapes have been consumed since prehistoric times and were one of the earliest domesticated fruit crops.1,13 According to ancient Mediterranean culture, the “vine sprang from the blood of humans who had fought against the gods.”14 But according to archaeological evidence, domestication took place about 5,000 years ago somewhere between the Caspian and Black Seas, and spread south to modern-day Syria, Iraq, Jordan, and Egypt before moving towards Europe.5,13 After the collapse of the Roman Empire in the 5th century, when Christianity became dominant, wine was associated with the Church and the monasteries soon perfected the process of making wine.1 About 300 years ago, Spanish explorers introduced the grape to what is now the United States, and California’s temperate climate proved to be an ideal place for grape cultivation.1 The grape is, famously, the most common ingredient in wine-making. A naturally-occurring symbiotic yeast grows on the grapes, making them easier to ferment and well-suited to the wine-making process.4 Popular wine cultivars of V. vinifera include Cabernet Sauvignon, Merlot, Chardonnay, Sauvignon Blanc, Vermentino, and Viognier.10 Wine often has been used as a medium for herbal remedies, due to the solvent nature of the alcohol. Both the Chinese and Western traditions made use of medicated wines (though ancient recipes in China, which date to the Shang Dynasty [ca 1600-1046 BCE], would have been made with rice [Oryza sativa, Poaceae] wine rather than grape wine).15 Many aperitifs and liqueurs originally were digestive aids made with wine and fortified with herbs such as wormwood (Artemisia absinthium, Asteraceae) and anise seed (Pimpinella anisum, Apiaceae).16 Medicated wines are less potent and usually require a higher dosage than tinctures made with higher-proof alcohol. Grapes are generally sweet and are used as table grapes, juice, jam, jelly, or for wine-making.13,17 About 99% of the world’s wine comes from V. vinifera.14 Grapes can also be dried in the vineyard and turned into raisins. To accomplish this, ripe grapes are plucked from the vine and placed on paper trays for two to four weeks. Afterwards, they are sent to the processing plant to be cleaned, packaged, and shipped.5 Modern Research Grapes have been the subject of numerous studies focused on many of their bioactive compounds, including flavonoids, stilbenes, and phenolic acids. Researchers have observed antioxidant, anti-tumor, immune modulatory, anti-diabetic, anti-atherogenic, anti-infectious, and neuro-protective properties of the fruit.11 Research suggests that grape product consumption could possibly benefit those with cancer, diabetes, and cardiovascular disease, which are among the leading causes of death worldwide.18 However, more human studies are needed to support any of these purported benefits. An in vitro study showed that antioxidants from a variety of grape product extracts performed as well as or better than BHT, tocopherol, and trolox in radical scavenging activity, metal chelating activity, and inhibition of lipid peroxidation.7 Water and ethanol seed extracts had the highest amount of phenolic compounds of any of the extracts used in the study. Grape seed extract (GSE), which has a growing body of study behind it, has gained attention for its possible use in lowering blood pressure and reducing the risk of heart disease, especially in pre-hypertensive populations.19 Unlike grape skins, where only red grapes contain anthocyanins, seeds from both white and red grape contain beneficial compounds. A standardized GSE made from white wine grapes recently was studied for its effects on gastrointestinal inflammation.20 While most studies focus on GSE and cardiovascular health, the preliminary results were promising enough to warrant a future human trial. Cardiovascular Disease Polyphenols have been found to protect the body from inflammation, which is common in people with heart disease.11 In a recent meta-analysis, the acute effects of polyphenols on the endothelium (inner lining of the blood vessels) were investigated. The analysis found that blood vessel function significantly improved in healthy adults in the initial two hours after consuming grape polyphenols.21 Another analysis found that the polyphenol content in every part of the grape — fruit, skin, and seed — had cardioprotective effects.22 In animal, in vitro, and limited human trials, grapes showed beneficial actions against oxidative stress, atherosclerosis (plaque build-up in arteries), high blood pressure, and ventricular arrhythmia (irregular heartbeat). Cancer Chemopreventive Effects Although the causes of and treatments for cancer are complex and multifaceted, studies have been done on the antioxidant activity of polyphenols and their cancer chemopreventive effects. These antioxidants demonstrate the ability to protect the body from cancer-causing substances and to prevent tumor cell growth by protecting DNA and regulating natural cell death.8,11,23 Diabetes In a randomized, double-blind controlled clinical study, healthy overweight/obese first degree relatives to type 2 diabetic patients were given grape polyphenols to counteract a high-fructose diet. After nine weeks of supplementation, grape polyphenols protected against fructose-induced insulin resistance.24 In another study, diabetic patients who consumed a dealcoholized Muscadine grape wine had reduced fasting insulin levels and increased insulin resistance.25 Nutrient Profile26 Macronutrient Profile: (Per 150 g [approx. 1 cup] grapes) 104 calories 1.1 g protein 27.3 g carbohydrate 0.2 g fat Secondary Metabolites: (Per 150 g [approx. 1 cup] grapes) Excellent source of: Vitamin K: 22 mcg (27.5% DV) Good source of: Potassium: 288 mg (8.2% DV) Vitamin C: 4.8 mg (8% DV) Thiamin: 0.1 mg (6.7% DV) Riboflavin: 0.1 mg (5.9% DV) Dietary Fiber: 1.4 g (5.6% DV) Manganese: 0.1 mg (5.5% DV) Vitamin B6: 0.1 mg (5% DV) Also provides: Phosphorus: 30 mg (3% DV) Magnesium: 11 mg (2.8% DV) Iron: 0.5 mg (2.8% DV) Vitamin A: 100 IU (2% DV) Niacin: 0.3 mg (1.5% DV) Vitamin E: 0.3 mg (1.5% DV) DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000-calorie diet. Recipe: Rosemary-Roasted Grapes and Cashew Cheese Crostini Ingredients: 1 cup raw cashews 1-2 cloves of garlic, minced 1/4 cup water 1/4 cup freshly-squeezed lemon juice, divided 1/2 teaspoon kosher or fine sea salt 1 pound seedless red grapes, washed and removed from stem 3 tablespoons olive oil, plus more for garnish 1 tablespoon fresh rosemary leaves, minced Salt and pepper to taste 1 small baguette or other loaf, sliced diagonally in 1/4 inch thick slices Directions: Soak cashews in enough water to cover by an inch for at least 4 hours. Drain. Make cashew “cheese” by placing soaked cashews, garlic, water, 2 tablespoons of lemon juice, and salt into a food processor and blend until smooth. Heat oven to 400°F. In a baking dish, mix grapes, olive oil, remaining lemon juice, rosemary, salt, and pepper. Place on center rack and roast 10-12 minutes or until skins are soft. Remove and set aside. Move the oven rack to the top setting and increase the heat to broil. Arrange bread slices in a single layer on a baking sheet and place in oven to toast for 1-3 minutes, monitoring carefully to prevent burning. Assemble crostini by spreading each toast with a layer of cashew cheese and topping with the grape mixture. Sprinkle with salt and drizzle with olive oil. Serve warm. References 1. Murray MT, Pizzorno J, Pizzorno L. The Encyclopedia of Healing Foods. New York, NY: Atria Books; 2005. 2. Yang J, Xiao YY. Grape phytochemcials and associated health benefits. Critical Reviews in Food Science and Nutrition. 2013;53:1202-1225. 3. Damrosch B. Grapes. In: The Garden Primer: Second Edition. New York, NY: Workman Publishing; 2008:353-359. 4. Wood R. The New Whole Foods Encyclopedia: A Comprehensive Resource for Healthy Eating. New York, NY: Penguin Books; 1999. 5. Ensminger AH, Ensminger ME, Konlande JE. The Concise Encyclopedia of Foods & Nutrition. Boca Raton, FL: CRC Press; 1995. 6. Tiwari B, Brunton NP, Brennan CS. Handbook of Plant Food Phytochemicals. London, UK: John Wiley & Sons, Ltd; 2013. 7. Keser S, Celik S, and Turkoglu S. Total phenolic contents and free-radical scavenging activities of grape (Vitis vinifera L.) and grape products. International Journal of Food Sciences and Nutrition. 2013;64(2):210-216. 8. Lila MA. Anthocyanins and human health: An in vitro investigative approach. J Biomed Biotechnol. 2004;2004(5):306-313. 9. Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food and Chemical Toxicology. 2002;40:599-607. 10. Burin VM, Ferreira-Lima NE, Panceri CP, Bordignon-Luiz MT. Bioactive compounds and antioxidant activity of Vitis vinifera and Vitis labrusca grapes: Evaluation of different extraction methods. Microchemical Journal. 2014;114:155-163. 11. Yadav M, Jain S, Bhardwaj A, et al. Biological and medicinal properties of grapes and their bioactive constituents: An update. Journal of Medinical Food. 2009;12(3):473-484. 12. Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition. 2004;32(12):1377-1382. 13. Myles S, Boyko AR, Owens CL, et al. Genetic structure and domestication history of the grape. Proceedings of the National Academy of Science of the United States of America. 2011;108(9):3530-3535. 14. McGovern PE. Ancient Wine: The Search for the Origins of Viniculture. Princeton, NJ: Princeton University Press; 2007. 15. Chan K, Cheung L. Interactions Between Chinese Herbal Medicinal Products and Orthodox Drugs. Boca Raton, FL: CRC Press; 2000. 16. Hoffmann D. The Herbal Handbook: A User’s Guide to Medical Herbalism. Rochester, VT: Inner Traditions; 1998. 17. Onstad D. Whole Foods Companion: A Guide for Adventurous Cooks, Curious Shoppers, and Lovers of Natural Foods. White River Junction, VT: Chelsea Green Publishing; 2004. 18. The top 10 causes of death – fact sheet no. 310. World Health Organization website. May 2014. Available here. Accessed November 23, 2015. 19. Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. Br J Nutr. 2015;16:1-13. 20. Starling S. White wine extract shows gastro benefits in vitro. Clinicals planned for 2016. NutraIngredients-USA website. November 12, 2015. Available here. Accessed November 19, 2015. 21. Li SH, Tian HB, Zhao HJ, Chen LH, Cui LQ. The acute effects of grape polyphenols supplementation on endothelial function in adults. PLOS ONE. 2013;8(7):e69818. 22. Leifert WR, Abeywardena MY. Cardioprotective actions of grape polyphenols. Nutrition Research. 2008;28:729-737. 23. Waffo-Téguo P, Hawthorne ME, Cuendet M, et al. Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures. Nutrition and Cancer. 2001;40(2):173-179. 24. Hokayem M. Grape polyphenols prevent fructose-induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients. Diabetes Care. 2013;36:1455-1461. 25. Banini AE, Boyd LG, Allen JG, Allen HG, Sauls DL. Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects. Nutrition. 2006;22:1137-45. 26. Basic Report: 09132, Grapes, red or green (European type, such as Thompson seedless), raw. United States Department of Agriculture, Agricultural Research Service. Available here. Accessed November 19, 2015.