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Spinach

Scientific Name(s): Spinacia oleracea L.
Common Name(s): Spinach

Clinical Overview

Use

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 immune and neurological systems. It has also been investigated in satiety trials for curbing hunger and reducing the desire for salty and sweet snacks. Although dosage forms of spinach other than its natural state as food are available, none can be reliably recommended due to a lack of quality clinical trials.

Dosing

Clinical evidence is lacking to provide a specific therapeutic dosage of spinach. As a food, spinach has received generally recognized as safe (GRAS) status by the US Food and Drug Administration (FDA).

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

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. Cross-sensitivity to beets and chard has been reported, and a common allergenic protein has been identified in spinach and tomatoes that can lead to angioedema and urticaria. Gout may be precipitated in predisposed individuals because of the purine content in spinach. Consumption of spinach in infants younger than 4 months is not recommended because calcium absorption may be decreased.

Toxicology

No data.

Botany

The Chenopodiaceae family consists of 100 species of evergreen or semi-evergreen 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 cool, moist seasons. There are many varieties of spinach, all of which have large, dark-green leaves on upright plants. The leaves are the most frequently used part of spinach.Sanders 2001, USDA 2007

Chemistry

Spinach contains a number of antioxidants, including carotenoids, polyphenols,Bakshi 2004, Pool-Zobel 1997 and flavonoids (quercetin).Torres-Sánchez 2000 The carotenoids are composed of 2 main classes, carotenes (beta-carotene) and xanthophylls (lutein).Richer 2000 Glycolipids (sulfoquinovosyl diacylglycerol) are found in the chloroplast membrane.Kuriyama 2005 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 in cooking methods also contribute to variations.Chung 2004, Hannon-Fletcher 2004, Kopsell 2006, McKillop 2002, Tang 2005 Spinach also contains oxalates and nitrates that may have negative effects.Betsche 2005, Brogren 2003, Chen 2003, Tamme 2006

Uses and Pharmacology

Activity of spinach has mostly been attributed to its antioxidant mechanisms.Ayes 2004, Hammond 1997, Hughes 2001, Richer 2000 While consumption of spinach significantly increases the levels of plasma lutein, changes in plasma beta-carotene, retinol, and the metabolite retinoic acid are not significant, and the antioxidant capacity of plasma does not increase.Rühl 2008, Schirrmacher 2010

Bone density

Animal data

A 12-week study in a rat model of osteopenia found that 750 and 1,000 mg/kg/day doses of spinach extract reversed bone loss and demonstrated effects on trabecular bone similar to estrogen therapy. The extract also attenuated weight gain.Adhikary 2017

Clinical data

An epidemiological study among young Japanese women found an association between low bone mass and reduced daily intake of yellow and green vegetables.Fujii 2009

Cancer

Several epidemiological studies suggest an association between spinach consumption and the inhibition of cancerBertone 2001, Kirsh 2007, Kotake-Nara 2001, Longnecker 1997, Slattery 2000, Torres-Sánchez 2000; however, in vitro experiments and clinical studies evaluating the potential role of spinach and/or spinach extracts in cancer are limited.Kuriyama 2005, Lomnitski 2003

Animal and in vitro data

An antioxidant extract derived from spinach leaves reduced papilloma multiplicity in a mouse model (P<0.01).Nyska 2001 This same extract has been used in several experiments and demonstrated a dose-dependent inhibitory effect on human prostate cancer cell proliferation.Asai 2004, Bakshi 2004, Kotake-Nara 2001, Lomnitski 2003 Certain fractions of spinach extracts exert a suppressive effect on gastric cancer cell cycle proliferation.Kuriyama 2005, Maeda 2005, Maeda 2007 Spinach glycoglycerolipids have been shown to inhibit angiogenesis in human cell lines and in mouse tumor models.Maeda 2011

Clinical data

Tomato juice, carrot juice, and spinach powder given daily to healthy volunteers for a 2-week period suppressed DNA strand breaks, a finding that supports the hypothesis that carotenoid-containing plant products exert a cancer-protective effect via a decrease in oxidative and other damage to human DNA.Pool-Zobel 1997

Cardiovascular disease

Clinical data

Analysis of the landmark Framingham Heart Study showed that an increased consumption of fruits and vegetables, the dominant sources 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 concentrationCastenmiller 2000; however, spinach is only one of many potential dietary options.

Spinach and other green leafy vegetables are the richest sources of dietary nitrate and can augment nitric oxide (NO) status, a critical regulator of endothelial function.Bondonno 2012, Liu 2013 Because flavonoids have been shown to increase endogenous endothelial NO production, a randomized, controlled, crossover trial investigated the acute effects of nitrate-rich spinach and flavonoid-rich apples on NO status and endothelial function in 30 healthy adults. A significant interaction was observed on plasma nitrosylated species, nitrite levels, and nitric oxide with apple (120 g apple flesh plus 80 g apple skins) and spinach (200 g thawed spinach) interventions; the effects were different when apple and spinach interventions were consumed together versus individually (P<0.001). Compared with controls, consumption of apple, spinach, and apple plus spinach test meals resulted in higher levels of all 3 nitrogen parameters (NO status), flow-mediated dilatation of the brachial artery, systolic blood pressure, and pulse pressure. However, contrary to the hypothesis, the combination of apples and spinach did not result in an additive or synergistic effect on NO status or endothelial function.Bondonno 2012 Similarly, in another randomized, controlled, crossover trial conducted in healthy adults (N=26; 20 women), consumption of a spinach test meal (250 g of cooked spinach containing nitrate 220 mg) improved overall acute pulse pressure and systolic blood pressure, as well as large artery elasticity, cardiac ejection time, estimated cardiac output, estimated stroke volume, and total vascular impedance.Liu 2013 In contrast to studies conducted in healthy participants, a short-term, randomized, controlled, crossover trial in 41 adults with high-normal blood pressure showed no beneficial effects of a nitrate-rich diet on blood pressure or arterial stiffness. Participants not taking antihypertensive medication consumed a high-nitrate diet (mean, 400 mg/day of nitrate) for 7 days that included 250 g/day of frozen spinach and 120 g/day of fresh green leafy salad vegetables (ie, lettuce, spinach, salad rocket). After 7 days, an increase in salivary and plasma nitrate and nitrite levels were observed compared to a low-nitrate diet; however, no effects were observed on blood pressure, heart rate, or measures of arterial stiffness.Bondonno 2014

CNS effects

Animal data

Studies in rats have demonstrated that spinach extracts are effective in preventing cognitive deficits and in reversing age-related motor and cognitive CNS deficits.Joseph 1998, Joseph 1999

An improvement in delayed eyeblink conditioning (an Alzheimer disease model) has been demonstrated in rats fed spinach.Cartford 2002 Mechanisms by which spinach acts are thought to be related to modulation of age-related increases in inflammatory response.Cartford 2002, Youdim 2001

Clinical data

A randomized, controlled crossover study (N=30) conducted in healthy volunteers found no short-term positive or negative effect on cognitive function or mood measures subsequent to a test meal that included spinach, apple, or apple plus spinach compared with control. Total quercetin glycosides and (-)-epicatechin content provided by the apple was 184 mg and 180 mg, respectively, whereas spinach provided 182 mg of nitrate. An increase in nitrosothiols and other nitro species was confirmed in saliva and urine samples; however, this short-term augmentation of nitric oxide status did not result in short-term CNS improvements.Bondonno 2014

Exercise-induced oxidative stress

Clinical trials

In an open, randomized, placebo-controlled trial (N=20), consumption of 1 g/kg/day of fresh spinach for 14 days by healthy young men significantly increased total antioxidant capacity compared with baseline and placebo. Compared to the placebo group, increases in total antioxidant capacity were observed in the spinach group before (P=0.001) and after (P=0.016) exercise. Increases in oxidative stress and muscle injury parameters in the placebo group were mitigated with consumption of spinach such that malondialdehyde, protein carbonyls, uric acid, and creatine kinase were significantly lower at multiple time points postexercise.Bohlooli 2015

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.Hughes 2001

Metabolic dysfunction

Clinical data

In a 2-day, double-blind, randomized, placebo-controlled crossover satiety study in 60 overweight or obese adults, administration of 5 g of a commercially available spinach extract did not significantly affect triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids, or high-sensitivity C-reactive protein. However, fasting and postprandial glucose was significantly reduced with spinach extract supplementation compared with placebo (P<0.01).Rebello 2015 In another controlled study (n=14), effects of spinach on postprandial glycemic and lipidemic responses were evaluated in normal weight and obese (but otherwise healthy) young adults. Participants (20 to 35 years of age) received 3 test meals, with a 1-week washout between each. Consumption of 75 g of boiled spinach (100 g fresh) with a fat-rich meal (bread and butter) was found to have no effect on postprandial glucose, serum insulin, triglyceride, LDL, or HDL levels compared with the bread and butter alone meal in either the normal weight or obese participants. However, in obese participants, a significantly smaller decrease in alpha-tocopherol/lipid was observed after the spinach plus bread/butter meal than the bread/butter meal (P<0.05), an effect not seen in the normal weight subjects.Maruyama 2013

Ophthalmic effects

Studies in the 1940s and 1950s showed that xanthophylls improved night vision and adaptation to dusk.Richer 2000 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.

Clinical data

Studies have shown that diets rich in lutein and zeaxanthin may lower the risk for age-related macular degeneration and may have a role in cataract prevention. Inhibition of lipid peroxidation and its chemical oxidation by free radicals is the suggested mechanism of action.Ayes 2004, Hammond 1997, Richer 2000 One study compared the effects of lutein- and zeaxanthin-rich foods and supplements on macular pigment level (MPL). Both dietary consumption of spinach powder and administration of lutein and zeaxanthin supplements for 8 weeks in healthy adults resulted in a change in serum lutein and zeaxanthin that was associated with a change in MPL. This effect was most obvious in participants with low baseline MPL. No effects on inflammation and oxidation markers were observed.Graydon 2012

Satiety

Animal and in vitro data

Membrane proteins (thylakoids) from the leaves of spinach have been evaluated in rats for their effects on satiety. Thylakoids inhibit the lipase/colipase hydrolysis of triacylglycerols in vitro, and suppress food intake, reduce body weight gain, and raise the satiety hormone cholecystokinin in rats.Köhnke 2009

Clinical data

In a study of healthy adults (N=11) given a high-fat meal with or without the addition of thylakoids, the satiety hormones cholecystokinin and leptin were reduced and the hunger hormone ghrelin was reduced after a single meal enriched with thylakoids.Köhnke 2009 In 2 double-blind, randomized, controlled, crossover studies conducted with thylakoids extracted from spinach cell walls, spinach extract significantly reduced hunger (P<0.01) in healthy normal weight and overweight adults.Rebello 2015, Stenblom 2015 Compared with placebo, satiety and hunger as well as craving for snacks were decreased acutely by administration of spinach extract (5 g of thylakoids equivalent to 100 g of spinach) prior to a test meal in 22 nonobese healthy Swedish women 40 to 70 years of age. A desire for salty snacks remained lower from 60 minutes to 360 minutes after the intervention, whereas the decrease in yearning for sweet snacks started at 15 minutes and continued for 420 minutes after intervention.Stenblom 2015 In a study of 60 overweight or obese adults, 5 g of a commercially available spinach extract given before lunch significantly reduced hunger (P=0.04), increased fullness (P=0.04), reduced longing for food (P<0.01), and reduced prospective intake (P=0.01) compared with placebo. Although thirst and the desire for salty or savory snacks were also reduced significantly, the desire for sweets was not. No significant differences were observed in subsequent intake at dinner, in "liking" (affective reaction reflecting a pleasant feeling at the consumption of food) and "wanting" (underlying drive that mediates the desire to consume a food) assessments 4 hours after the meal, or in triglycerides, total cholesterol, HDL, LDL, free fatty acids, and high-sensitivity C-reactive protein. However, fasting and postlunch glucose levels were significantly reduced with spinach extract supplementation (P<0.01).Rebello 2015

Tooth sensitivity

Clinical data

In a 12-week, randomized controlled trial (N=60), use of an herbal toothpaste twice daily that contained 10 g of spinach, a number of other herbs, and potassium nitrate (a known desensitizer) improved dental sensitivity to air and cold water compared with baseline and with a placebo dentrifice (without potassium nitrate). The herbs included in the spinach formulation were reported to have bactericidal properties that protect against periodontal pathogens, gingivitis, plaque, and bad breath, although these effects were not tested in the study. Although the authors declared that spinach and potassium nitrate were responsible for reducing dental hypersensitivity because these agents were lacking in the control, neither the study design nor the resulting data provided any support for that claim. No adverse effects were observed.Kumari 2013

Vaccine

Spinach is being investigated as a plant-derived, edible vehicle for anthrax vaccineSussman 2003 as well as a vehicle for the HIV-1 Tat protein, a prospective vaccine candidate.Karasev 2005

Dosing

Clinical evidence is lacking to provide a specific therapeutic dosage of spinach. As a food, spinach has GRAS status; however, overconsumption may pose a potential risk because of the high nitrate content of spinach.Lomnitski 2003

Pregnancy / Lactation

GRAS when used as food. Avoid dosages higher than 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 international normalized ratio (INR) in patients taking warfarinBandolier 2001; 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.Bohn 2004, Karlson 1986, Schurgers 2004

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 observed in experiments.Betsche 2005, Genannt Bonsmann 2008, Sanchez 1997

Antigenotoxicity activity has been demonstrated via inhibition of cytochrome P450 1A2 enzyme in vitro. Little is known regarding in vivo effects.Rodríguez-Fragoso 2011

Adverse Reactions

Allergic reactions to spinach are rare, with very few case reports in the literature.Ferrer 2011, Foti 2012, Sanchez 1997 Immunoglobulin E–mediated allergy to spinachSanchez 1997 and sensitization to spinach powderSchuller 2005 have been reported. Cross-reactivity to molds, mushrooms, beets, chard, and latex have been described, making it difficult to implicate spinach.Ferrer 2011, Herrera 2002, Herrera-Mozo 2006, Maillard 2000, Schuller 2005 However, cross-reactivity with beets and chard was confirmed with skin prick testing and immunoglobulin E binding assays in an 18-month-old boy who presented with perioral rash and generalized urticaria after eating spinach.Ferrer 2011 Additionally, spinach contains histamine, which can cause pseudoallergic reactions.Schuller 2005 Proteomic analysis of spinach and tomato identified a common allergenic protein, Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase), that led to severe oral angioedema in a 23-year-old nonatopic female after consuming spinach leaves; she had a history of urticaria and angioedema after ingestion of raw or cooked spinach and tomato.Foti 2012

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, which is caused by high levels of uric acid.Bandolier 2007, Ozçakar 2003 Spinach is not recommended in infants younger than 4 months because the oxalate content may reduce calcium absorption.Betsche 2005, Brogren 2003, Chen 2003 Large quantities of spinach and rhubarb were implicated as dietary sources of oxalate in a case of acute oxalate nephropathy secondary to orlistat-induced enteric hyperoxaluria in a 60-year-old obese woman with diabetes, hypothyroidism, gastroesophageal reflux, and renal colic.Kwan 2013 Methemoglobin formation is also possible through the plant's nitrate content.Tamme 2006

Toxicology

There is little or no information regarding toxicity 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.Lomnitski 2003 Spinach has been implicated in outbreaks of Escherichia coli food poisoning, including the autumn 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.Berger 2010, Doyle 2008, Heaton 2008, Morgan 2007

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