Spinach

Scientific Name(s): Spinacia oleracea L. Family: Chenopodiaceae

Common Name(s): Spinach

Uses

Many of the reported actions of spinach are related to its antioxidant properties. It may play a role in the prevention of cancer, cardiovascular disease, age-related macular degeneration, and the degeneration of the immune and neurological systems.

Dosing

There is no clinical evidence to support a specific therapeutic dosage of spinach. As a food, spinach has US Food and Drug Administration (FDA) generally recognized as safe (GRAS) status.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

GRAS when used as food. Avoid dosages above those found in food because safety and efficacy are unproven.

Interactions

Bioavailability of vitamin K from spinach is limited. While a simple meal containing spinach can result in a statistically significant reduction in the international normalized ratio (INR), the decrease is not likely to be clinically important. Absorption of magnesium, calcium, and zinc, but not nonheme iron, may be decreased by concurrent consumption of oxalates in spinach.

Adverse Reactions

Allergic reactions to spinach are rare. Gout may be precipitated in predisposed individuals because of the purine content. Consumption of spinach in infants younger than 4 months is not recommended because of the potential for reduced calcium absorption. Contamination with Escherichia coli has resulted in outbreaks of food-borne illness.

Toxicology

Research reveals little or no information regarding toxicology with the use of spinach.

Botany

The Chenopodiaceae family consists of 100 species of evergreen or semievergreen annuals, perennials, and shrubs. Other members of this group include beet and chard. In temperate climates, spinach reaches edible maturity quickly (37 to 45 days) and thrives best during the cool, moist seasons of the year. There are a number of varieties of spinach, all of which have large, dark-green leaves on upright plants. The leaves are the most frequently used part of spinach. 1 , 2

Chemistry

Spinach contains a number of antioxidants, including carotenoids, polyphenols, 3 , 4 and flavonoids (quercetin). 5 The carotenoids are composed of 2 main classes, carotenes (beta-carotene) and xanthophylls (lutein). 6 Glycolipids (sulfoquinovosyl diacylglycerol) are found in the chloroplast membrane. 7 Spinach is regarded as a valuable dietary source of vitamin A, nonheme iron, folate, and lutein. Studies show much intrinsic variation in the bioavailability of these substances and variations caused by cooking methods. 8 , 9 , 10 , 11 , 12 Spinach also contains oxalates and nitrates that may have negative effects. 13 , 14 , 15 , 16

Uses and Pharmacology

Activity of spinach has mostly been attributed to its antioxidant mechanisms. 6 , 17 , 18 , 19 Although consumption of spinach increases the levels of plasma lutein, nonsignificant changes in plasma beta-carotene, retinol, and the metabolite retinoic acid have been noted, while the antioxidant capacity of plasma has not been shown to increase. 20 , 21

Cancer

Several epidemiological studies suggest an association between spinach consumption and the inhibition of cancer. 5 , 22 , 23 , 24 , 25 , 26 In vitro experiments and clinical studies evaluating the potential role of spinach and/or spinach extracts in cancer are limited. 7 , 27

Animal data

An antioxidant extract derived from spinach leaves reduced the multiplicity of papillomas in a mouse model ( P < 0.01). 28 This same extract has been used in several experiments demonstrating a dose-dependent inhibitory effect on human prostate cancer cell proliferation. 4 , 23 , 27 , 29 Certain fractions of spinach extracts exert a suppressive effect on gastric cancer cell cycle proliferation. 7 , 30 , 31 Spinach glycoglycerolipids have been shown to inhibit angiogenesis in human cell lines and in mouse tumor models. 32

Clinical data

Tomatoes, carrots, and spinach powder given daily to healthy volunteers for a 2-week period suppressed DNA strand breaks. It has been proposed that these plant products exert their cancer-protective effect via a decrease in oxidative and other damage to human DNA. 3

Cardiovascular disease

Analysis of the landmark Framingham Heart Study showed that an increased consumption of fruits and vegetables, the dominant source of folate in the human diet, was associated with higher levels of plasma folate, lower levels of plasma homocysteine, and a reduced risk of cardiovascular disease. Spinach consumption can increase plasma folate concentration 33 ; however, spinach is only one of many potential dietary factors.

CNS effects
Animal data

Studies in rats have demonstrated that spinach extracts are effective in preventing cognitive deficits and reversing age-related motor and cognitive CNS deficits. 34 , 35

An improvement in delayed eye-blink conditioning (an Alzheimer disease model) has been demonstrated in rats fed spinach. 36 Mechanisms by which spinach might act are related to modulation of age-related increases in inflammatory response. 36 , 37

Clinical data

There are no clinical data regarding the use of spinach for neurological dysfunction.

Ophthalmic effects

Studies in the 1940s and 1950s showed that xanthophylls improved night vision and adaptation to dusk. Lutein and zeaxanthin, abundant in green leafy vegetables such as spinach, are highly concentrated in the macula of the eye and are believed to limit tissue damage by absorbing blue light.

Animal data

There are no animal data regarding the use of spinach for age-related macular degeneration.

Clinical data

Studies have shown that diets rich in lutein and zeaxanthin may lower the risk for age-related macular degeneration and could have a role in cataract prevention. Inhibition of lipid peroxidation and its chemical oxidation by free radicals is the suggested mechanism of action. 6 , 17 , 18

Other
Bone density

An epidemiological study among young Japanese women found an association between low bone mass and reduced daily intake of yellow and green vegetables. 38

Immune system effects

Spinach is a dietary source of the carotenoid antioxidants beta-carotene and lutein, and thus, is postulated to help maintain immune cell integrity by reducing reactive oxygen species. 19

Satiety

Membrane proteins (thylakoids) from the leaves of spinach have been evaluated in rats and healthy adults for effect on satiety. In rats, hydrolysis of triacylglycerols suppressed food intake, and reductions in body weight gain have been observed. In adults, satiety hormones cholecystokinin and leptin were reduced and the hunger hormone ghrelin was reduced after a single meal enriched with thylakoids. 39

Vaccine

Spinach is being investigated as a plant-derived, edible vehicle for anthrax vaccine, 40 as well as a vehicle for the HIV-1 Tat protein, a prospective vaccine candidate. 41

Dosage

There is no clinical evidence to a support a specific therapeutic dosage of spinach. As a food, spinach has GRAS status; however, overconsumption may pose a potential risk because of the presence of nitrates in the vegetable. 27

Pregnancy/Lactation

GRAS when used as food. Avoid dosages above those found in food because safety and efficacy have not been established.

Interactions

Warfarin interferes with the hepatic synthesis of vitamin K-dependent coagulation factors. Fluctuations in vitamin K intake can cause changes in anticoagulant response. Because spinach has a high vitamin K content, it can decrease the INR in patients taking oral anticoagulants 42 ; however, bioavailability of the vitamin K content is low. Studies in patients receiving warfarin with single meals of spinach resulted in a statistically significant, but not clinically important, reduction in the INR. 43 , 44 , 45

Absorption of magnesium, calcium, and zinc may be decreased by concurrent consumption of oxalates. Decreases in magnesium absorption have been demonstrated in healthy adults, but this is likely to be offset by the magnesium content of spinach. No decrease in nonheme iron absorption by oxalates has been shown in experiments. 14 , 46 , 47

Adverse Reactions

Allergic reactions to spinach are rare, with very few case reports in the literature. 47 Immunoglobulin E–mediated allergy to spinach 47 and sensitization to spinach powder 48 have been reported. Crossreactivity to molds, mushrooms, and latex have been described, making it difficult to implicate spinach. 48 , 49 , 50 , 51 Additionally, spinach contains histamine, which can cause pseudoallergic reactions. 48 Because uric acid is a product of purine catabolism and spinach contains moderate amounts of purines, dietary reduction of purine intake may be appropriate in individuals predisposed to gout. 52 , 53 Spinach is not recommended in infants younger than 4 months because the oxalate content could reduce calcium absorption. 13 , 14 , 15 Methemoglobin formation is also possible through the plant's nitrate content. 16 Spinach has been implicated in outbreaks of E. coli food poisoning, including the fall 2006 outbreak in the United States that resulted in approximately 100 hospitalizations and 3 deaths. Contamination may occur via organic fertilizers or irrigation water or in postharvesting processing and bagging. 54 , 55 , 56

Toxicology

There is little or no information regarding toxicology with the use of whole spinach leaves. An antioxidant extract derived from spinach leaves was nonmutagenic. Toxicological studies performed on this extract in mice, rats, and rabbits showed no toxicity, adverse reactions, or abnormalities. 27

Bibliography

1. Spinacia oleracea L. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , 1 June 2007). National Plant Data Team, Greensboro, NC 27401-4901 USA.
2. Sander DC . Spinach. North Carolina State University. North Carolina Cooperative Extension Service. Horticulture Information Leaflets . 2001 . http://www.ces.ncsu.edu/depts/hort/hil/hil-17.html . Accessed January 10, 2012.
3. Pool-Zobel BL , Bub A , Müller H , Wollowski I, Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods . Carcinogenesis . 1997;18(9):1847-1850.
4. Bakshi S , Bergman M , Dovrat S , Grossman S . Unique natural antioxidants (NAOs) and derived purified components inhibit cell cycle progression by downregulation of ppRb and E2F in human PC3 prostate cancer cells . FEBS Lett . 2004;573(1-3):31-37.
5. Torres-Sánchez L , López-Carillio L , López-Cervantes M , Rueda-Neria C , Wolff MS . Food sources of phytoestrogens and breast cancer risk in Mexican women . Nutr Cancer . 2000;37(2):134-139.
6. Richer S . Antioxidants and the eye . Int Ophthalmol Clin . 2000;40(4):1-16.
7. Kuriyama I , Musumi K , Yonezawa Y , et al. Inhibitory effects of glycolipids fraction from spinach on mammalian DNA polymerase activity and human cancer cell proliferation . J Nutr Biochem . 2005;16(10):594-601.
8. Tang G , Qin J , Dolnikowski GG , Russell RM , Grusak MA . Spinach or carrots can supply significant amounts of vitamin A as assessed by feeding with intrinsically deuterated vegetables . Am J Clin Nutr . 2005;82(4):821-828.
9. Kopsell DA , Lefesrud MG , Kopsell DE , Wenzel AJ, Gerweck C, Curran-Celentano J. Spinach cultigen variation for tissue carotenoid concentrations influences human serum carotenoid levels and macular pigment optical density following a 12-week dietary intervention . J Agric Food Chem . 2006;54(21):7998-8005.
10. Hannon-Fletcher MP , Armstrong NC , Scott JM , et al. Determining bioavailability of food folates in a controlled intervention study . Am J Clin Nutr . 2004;80(4):911-918.
11. McKillop DJ , Pentieva K , Daly D , et al. The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet . Br J Nutr . 2002;88(6):681-688.
12. Chung HY , Rasmussen HM , Johnson EJ . Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men . J Nutr . 2004;134(8):1887-1893.
13. Chen Z , Ye Z , Zeng L , Yang W . Clinical investigation on gastric oxalate absorption . Chin Med J (Engl) . 2003;116(11):1749-1751.
14. Betsche T , Fretzdorff B . Biodegradation of oxalic acid from spinach using cereal radicles . J Agric Food Chem . 2005;53(25):9751-9758.
15. Brogren M , Savage GP . Bioavailability of soluble oxalate from spinach eaten with and without milk products . Asia Pac J Clin Nutr . 2003;12(2):219-224.
16. Tamme T , Reinik M , Roasto M , Juhkam K , Tenno T , Kiis A . Nitrates and nitrites in vegetables and vegetable-based products and their intakes by the Estonian population . Food Addit Contam . 2006;23(4):355-361.
17. Hammond BR Jr , Johnson EJ , Russell RM , et al. Dietary modification of human macular pigment density . Invest Ophthalmol Vis Sci . 1997;38(9):1795-1801.
18. Ayes for your eyes. Cataracts and macular degeneration are two common eye problems. But you can lower the chances that they'll happen to you . Harv Health Lett . 2004;29(4):1-2.
19. Hughes DA . Dietary carotinoids and human immune function . Nutrition . 2001;17(10):823-827.
20. Schirrmacher G, Skurk T, Hauner H, Grassmann J. Effect of Spinacia oleraceae L. and Perilla frutescens L. on antioxidants and lipid peroxidation in an intervention study in healthy individuals. Plant Foods Hum Nutr . 2010;65(1):71-76.
21. Rühl R, Bub A, Watzl B. Modulation of plasma all-trans retinoic acid concentrations by the consumption of carotenoid-rich vegetables. Nutrition . 2008;24(11-12):1224-1226.
22. Longnecker MP , Newcomb PA , Mittendorf R , Greenberg ER , Willett WC . Intake of carrots, spinach and supplements containing vitamin A in relation to risk of breast cancer . Cancer Epidemiol Biomarkers Prev . 1997;6(11):887-892.
23. Kotake-Nara E , Kushiro M , Zhang H , Sugawara T, Miyashita K, Nagao A. Carotenoids affect proliferation of human prostate cancer cells . J Nutr . 2001;131(12):3303-3306.
24. Bertone ER , Hankinson SE , Newcomb PA , et al. A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States) . Cancer Causes Control . 2001;12(1):83-90.
25. Slattery ML , Benson J , Curtin K , Ma KN, Schaeffer D, Potter JD. Carotenoids and colon cancer . Am J Clin Nutr . 2000;71(2):575-582.
26. Kirsh VA, Peters U, Mayne ST, et al; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst . 2007;99(15):1200-1209.
27. Lomnitski L , Bergman M , Nyska A , Grossman S . Composition, efficacy, and safety of spinach extracts . Nutr Cancer. 2003;46(2):222-231.
28. Nyska A , Lomnitski L , Spalding J , et al. Topical and oral administration of the natural water-soluble antioxidant from spinach reduces the multiplicity of papillomas in the Tg.AC mouse model . Toxicol Lett . 2001;122(2-3):33-44.
29. Asai A , Terasaki M , Nagao A . An epoxide-furanoid rearrangement of spinach neoxanthin occurs in the gastrointestinal tract of mice and in vitro: formation and cytostatic activity of neochrome stereoisomers . J Nutr . 2004;134(9):2237-2243.
30. Maeda N , Hada T , Hada T , et al. Effects of DNA polymerase inhibitory and antitumor activities of lipase-hydrolyzed glycolipid fractions from spinach . J Nutr Biochem . 2005;16(2):121-128.
31. Maeda N , Hada T , Yoshida H , Mizushina Y . Inhibitory effect on replicative DNA polymerases, human cancer cell proliferation, and in vivo anti-tumor activity by glycolipids from spinach . Curr Med Chem . 2007;14(9):955-967.
32. Maeda N, Matsubara K, Yoshida H, Mizushina Y. Anti-cancer effect of spinach glycoglycerolipids as angiogenesis inhibitors based on the selective inhibition of DNA polymerase activity. Mini Rev Med Chem . 2011;11(1):32-38.
33. Castenmiller J , van de Poll C , West C , Brouwer IA, Thomas CM, van Dusseldorp M. Bioavailability of folate from processed spinach in humans . Ann Nutr Metab . 2000;44(4):163-169.
34. Joseph J , Shukitt-Hale B , Denisova NA , et al. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits . J Neurosci . 1998;18(19):8047-8055.
35. Joseph J , Shukitt-Hale B , Denisova NA , et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation . J Neurosci . 1999;19(18):8114-8121.
36. Cartford MC , Gemma C , Bickford PC . Eighteen-month-old fischer 344 rats fed a spinach-enriched diet show improved delay classical eyeblink conditioning and reduced expression of tumor necrosis factor (tnf) and tnf in the cerebellum . J Neurosci . 2002;22(14):5813-5816.
37. Youdim KA , Joseph JA . A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects . Free Radic Biol Med . 2001;30(6):583-594.
38. Fujii H, Noda T, Sairenchi T, Muto T. Daily intake of green and yellow vegetables is effective for maintaining bone mass in young women. Tohoku J Exp Med . 2009;218(2):149-54.
39. Köhnke R, Lindbo A, Larsson T, et al. Thylakoids promote release of the satiety hormone cholecystokinin while reducing insulin in healthy humans. Scand J Gastroenterol . 2009;44(6):712-719.
40. Sussman HE . Spinach makes a safer anthrax vaccine . Drug Discov Today . 2003;8(10):428-430.
41. Karasev AV , Foulke S , Wellens C , et al. Plant based HIV-1 vaccine candidate: Tat protein produced in spinach . Vaccine . 2005;23(15):1875-1880.
42. Things that affect our INR. Bandolier . May 2001 ;87(5). http://www.medicine.ox.ac.uk/bandolier/band87/b87-5.html . Accessed January 10, 2012.
43. Karlson B , Leijd B , Hellstrom K . On the influence of vitamin K-rich vegetables and wine on the effectiveness of warfarin treatment . Acta Med Scand . 1986;220(4):347-350.
44. Schurgers LJ , Shearer MJ , Hamulyak K , Stocklin E , Vermeer C . Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects . Blood . 2004;104(9):2682-2689.
45. Bohn T , Davidsson L , Walczyk T , Hurrell RF . Fractional magnesium absorption is significantly lower in human subjects from a meal served with an oxalate-rich vegetable, spinach, as compared with a meal served with kale, a vegetable with a low oxalate content . Br J Nutr . 2004;91(4):601-606.
46. gennant Bonsmann SS, Walczyk T, Renggli S, Hurrell RF. Oxalic acid does not influence nonhaem iron absorption in humans: a comparison of kale and spinach meals. Eur J Clin Nutr . 2008;62(3):336-341.
47. Sanchez I , Rodriguez F , Garcia-Abujeta JL , et al. Oral allergy syndrome induced by spinach . Allergy . 1997;52(12):1245-1246.
48. Schuller A , Morisset M , Maadi F , et al. Occupational asthma due to allergy to spinach powder in a pasta factory . Allergy . 2005;60(3):408-409.
49. Maillard H , Machet L , Meurisse Y , et al. Cross-allergy to latex and spinach . Acta Derm Venereol . 2000;80(1):51.
50. Herrera I , Moneo I , Caballero ML , et al. Food allergy to spinach and mushroom . Allergy . 2002;57(3):261-262.
51. Herrera-Mozo I, Ferrer B , Luis Rodriguez-Sanchez J , Juarez C . Description of a novel panallergen of cross-reactivity between moulds and foods . Immunol Invest . 2006;35(2):181-197.
52. Purines in foods. Bandolier . January 2007. http://www.medicine.ox.ac.uk/bandolier/booth/gout/purfood.html . Accessed January 10, 2012.
53. Ozçakar L , Oguz AK . Spinach attack: a funny turn in gouty arthritis . Rheumatol Int . 2003;23(6):327.
54. Doyle MP, Erickson MC. Summer meeting 2007 - the problems with fresh produce: an overview. J Appl Microbiol . 2008;105(2):317-30.
55. Heaton JC, Jones K. Microbial contamination of fruit and vegetables and the behaviour of enteropathogens in the phyllosphere: a review. J Appl Microbiol . 2008;104(3):613-26.
56. Berger CN, Sodha SV, Shaw RK, et al. Fresh fruit and vegetables as vehicles for the transmission of human pathogens. Environ Microbiol . 2010;12(9):2385-97.

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