Spinach

October 2007

Spinacia oleracea L. Family: Chenopodiaceae

Spinach

Uses

Many of the reported actions of spinach are related to 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 “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 the vitamin K content in spinach is limited. A simple meal containing spinach can result in a statistically significant reduction in the international normalized ratio (INR); however, the decrease is not likely to be clinically important. Absorption of magnesium, calcium, and zinc may be decreased by concurrent consumption of oxalates.

Adverse Reactions

Allergic reactions to spinach are rare. Gout may be precipitated in predisposed persons because of the purine content. Consumption of spinach in infants younger than 4 months of age is not recommended because of the potential for reduced calcium absorption.

Toxicology

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

The Chenopodiaceae family consists of 100 species of evergreen or semievergreen annuals, perennials, and shrubs. Other members of this group include beet and chard. 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 parts of spinach. ^1, , ²

Spinach contains a number of antioxidants including carotenoids, polyphenols, ^3, , ^4, and flavonoids (quercetin). ^5, The carotenoids are composed of 2 main classes, carotenes (betacarotene) 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 potential negative effects. ^13, , ^14, , ^15, , ¹⁶

Cancer Several epidemiological studies suggest an association between spinach consumption and cancer prevention. ^5, , ^17, , ^18, , ^19, , ^20, In vitro experiments and clinical studies evaluating the potential role of spinach and/or spinach extracts in cancer are limited. ^7, , ²¹

Animal data An antioxidant extract derived from spinach leaves reduced the multiplicity of papillomas in a mouse model ( P < 0.01). ^22, This same extract has been used in several experiments demonstrating a dose-dependent inhibitory effect on human prostate cancer cell proliferation. ^4, , ^18, , ^21, , ^23, Certain fractions of spinach extracts exert a suppressive effect on gastric cancer cell cycle proliferation. ^7, , ^24, , ²⁵

Clinical data Tomatoes, carrots, and spinach powder given daily to healthy volunteers for a 2-week period may have 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 ²⁶ ; however, spinach is probably only one of many 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. ^27, , ²⁸

An improvement in delayed eye-blink conditioning (associated with Alzheimer disease) has been demonstrated in rats fed spinach. ^29, Mechanisms by which spinach might act are suggested to be related to modulation of age-related increases in inflammatory response. ^29, , ³⁰

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, , ^31, , ³²

Other

Vaccine Spinach is being investigated as a plant-derived, edible vehicle for anthrax vaccine, ^33, as well as a vehicle for the HIV-1 Tat protein (a prospective vaccine candidate). ³⁴

Immune system effects Spinach is a source of dietary carotenoid antioxidants (beta-carotene and lutein), and thus is postulated to help maintain immune cell integrity by reducing the presence of reactive oxygen species. ³⁵

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. ²¹

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

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 ^36, ; 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. ^37, , ³⁸

Absorption of magnesium, calcium, and zinc may be decreased by concurrent consumption of oxalates. Significant decreases in magnesium absorption have been demonstrated in healthy adults, but this is likely to be offset by the magnesium content of the spinach. ^14, , ³⁹

Allergy to spinach is considered rare with very few case reports in the literature. ^40, immunoglobulin E (IgE)-mediated allergy to spinach ^40, and sensitization to spinach powder ⁴¹ have been reported.

Crossreactivity to molds, mushrooms, and latex have been described, making it difficult to implicate spinach. ^41, , ^42, , ^43, , ^44, Additionally, spinach contains histamine, which can cause pseudoallergic reactions. ^41, Because uric acid is a product of purine catabolism and spinach contains moderate amounts of purines, dietary measures to reduce purine intake may be appropriate in persons predisposed to gout. ^45, , ^46, Spinach is not recommended in infants younger than 4 months of age as the oxalate content could reduce calcium absorption. ^13, , ^14, , ^15, Methemoglobin formation is also possible through the plants nitrate content. ¹⁶

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. ²¹

1. Spinacia oleracea L. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , 1 June 2007). National Plant Data Center, Baton Rouge, LA 70874-4490 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 September 10, 2007.

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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. PubMed

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. PubMed

9. Kopsell DA , Lefesrud MG , Kopsell DE , et al. 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. PubMed

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. PubMed

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. PubMed

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. PubMed

13. Chen Z , Ye Z , Zeng L , Yang W . Clinical investigation on gastric oxalate absorption . Chin Med J (Engl) . 2003;116(11):1749-1751. PubMed

14. Betsche T , Fretzdorff B . Biodegradation of oxalic acid from spinach using cereal radicles . J Agric Food Chem . 2005;53(25):9751-9758. PubMed

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. PubMed

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. PubMed

17. 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. PubMed

18. Kotake-Nara E , Kushiro M , Zhang H , et al. Carotenoids affect proliferation of human prostate cancer cells . J Nutr . 2001;131(12):3303-3306. PubMed

19. 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. PubMed

20. Slattery ML , Benson J , Curtin K , et al. Carotenoids and colon cancer . Am J Clin Nutr . 2000;71(2):575-582. PubMed

21. Lomnitski L , Bergman M , Nyska A , Grossman S . Composition, efficacy, and safety of spinach extracts . Nutr Cancer. 2003;46(2):222-231. PubMed

22. 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.

23. 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. PubMed

24. 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. PubMed

25. 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. PubMed

26. Castenmiller J , van de Poll C , West C , et al. Bioavailability of folate from processed spinach in humans . Ann Nutr Metab . 2000;44(4):163-169. PubMed

27. 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. PubMed

28. Joseph J , Shukitt-Hale B , Shukitt-Hale B , 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. PubMed

29. 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. PubMed

30. 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. PubMed

31. 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. PubMed

32. 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.

33. Sussman HE . Spinach makes a safer anthrax vaccine . Drug Discov Today . 2003;8(10):428-430. PubMed

34. 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. PubMed

35. Hughes DA . Dietary carotinoids and human immune function . Nutrition . 2001;17(10):823-827. PubMed

36. Things that affect our INR. Bandolier . May 2001 ;87(5). http://www.jr2.ox.ac.uk/bandolier/band87/b87-5.html . Accessed September 10, 2007.

37. 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. PubMed

38. 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. PubMed

39. 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. PubMed

40. Sanchez I , Rodriguez F , Garcia-Abujeta JL , et al. Oral allergy syndrome induced by spinach . Allergy . 1997;52(12):1245-1246. PubMed

41. 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. PubMed

42. Maillard H , Machet L , Meurisse Y , et al. Cross-allergy to latex and spinach . Acta Derm Venereol . 2000;80(1):51. PubMed

43. Herrera I , Moneo I , Caballero ML , et al. Food allergy to spinach and mushroom . Allergy . 2002;57(3):261-262. PubMed

44. 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. PubMed

45. http://www.jr2.ox.ac.uk/bandolier/booth/gout/purfood.html .

46. Ozcakar L , Oguz AK . Spinach attack: a funny turn in gouty arthritis . Rheumatol Int . 2003;23(6):327. PubMed