Thuốc Strawberry

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Thuốc Strawberry
Thuốc Strawberry

Holevn Health share articles about :Thuốc Strawberry  , side effects – dosage , Thuốc Strawberry what disease treatment.Other noted issues. Please refer to the details below.

Scientific Name(s): Fragaria ananassa, Fragaria x ananassa, Duch.
Common Name(s): Strawberry

Medically reviewed by Holevn.org. Last updated on May 22, 2019.

Clinical Overview

Use

Wild strawberry has likely been used for thousands of years, based on evidence from pre-Columbian sites. Epidemiological and interventional studies reveal potential beneficial effects of strawberries on cellular inflammation and oxidation, some cardiometabolic disorders, immunomodulation, metabolic dysregulation, and some neurological conditions. Strawberries have been evaluated in some cancers, but clinical data are lacking to support use.

Dosing

Fresh strawberry dosages have ranged from 250 to 500 g/day, given for up to 1 month. Freeze-dried strawberry powder dosages have ranged from 10 to 60 g/day for up to 6 months. In clinical studies, 1 g of freeze-dried strawberries (at 10% of fresh weight) was equivalent to approximately 10 g of fresh strawberries.

Contraindications

Known allergy to strawberries; cross-sensitivity may occur in birch pollen–allergic individuals.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Allergic reactions (itching, dermatitis) to red ripe strawberries (but not the mutated white genotype) have been reported. A case report of a local reaction to an artificial strawberry-scented anesthetic face mask was reported in a 9-year-old girl. In clinical studies assessing adverse effects of dietary supplementation with strawberries, no adverse events occurred with 6 to 12 weeks of supplementation.

Toxicology

No data.

Scientific Family

  • Rosaceae

Botany

Strawberries (Fragaria spp) belong to the Rose (Rosaceae) family and grow across a broad range of temperate habitats and elevations. Fragaria has unusual fruit morphology in that it has an aggregate accessory fruit. The fruit, which is consumed, is a fleshy receptacle in which the botanical fruits (dry achenes) are embedded. The seed in the achene matures in a coordinated manner with the receptacle as it softens and expands. This low-growing herbaceous perennial is pollinated by insects and capable of clonal growth, and its accessory fruits are dispersed by animals. The leaves are usually evergreen and generally trifolioliate; however, Fragaria iinumae is deciduous, and some Chinese species have 5 leaflets. Flowers are white and can be tinged with pink. Nine related species (the China clade) are distributed throughout China, Himalayan countries, and Japan, while another 11 species (the vesca clade) are found in northern Eurasia, North and South America, and Hawaii.1

History

Wild strawberry has likely been consumed by humans for thousands of years; it grows throughout the Northern Hemisphere and in a disjunct manner in southern South America. Limited archaeobotanical evidence has uncovered strawberry achenes (seeds) from pre-Columbian sites in eastern North America. The Picunche and Mapuche people of Chile domesticated Fragaria chiloensis more than 1,000 years ago. In Europe, Fragaria vesca (the alpine strawberry) has been grown in gardens since at least Roman times, and the musk-flavored Fragaria moschata (hautboy) and Fragaria viridis (green strawberry) since the 16th century. The North and South American species Fragaria virginiana and F. chiloensis, which hybridize naturally in northwestern North America, are the parental species of the domesticated European F. x ananassa, which originated in the 18th century. Although strawberries have been primarily valued for their flavor, medicinal claims have been acknowledged for centuries. Strawberries are also valuable for demonstrating DNA extraction; the biological diversity of the strawberry lends itself to the study of ecological and evolutionary genomics. Based on fossil evidence found in Canada of a single achene dated approximately 2.9 million years ago, representing a remnant of Pliocene-Pleistocene Beringia, current species of Fragaria are estimated to have last shared a common ancestor between 1 and 4.1 million years ago.1, 2

F. x ananassa (pineapple or pine strawberry) garnered its name from the pineapple (Ananas) aroma of its fruit. F. x ananassa now dominates strawberry cultivation, with global strawberry production being twice that of all other berry crops and the majority of production (98%) occurring in the Northern Hemisphere. The United States is the leading producer, followed by Spain, Japan, Poland, Italy, and South Korea.1, 2 Although in the United States, strawberries are among the most common fruits in terms of production and consumption,3 consumption is somewhat tempered by reportedly high pesticide residue, and imported crops from Mexico, Chile, and China are common.1, 4 Strawberries are commonly consumed in fresh and frozen forms, as well as in processed products such as yogurts, juices, nectars, jams, and jellies. Extracts from strawberries have also been used in functional foods and dietary supplements. Over the last decade, human epidemiological and interventional studies with strawberries have increased; results reveal a range of potential beneficial effects on inflammation, cardiovascular disease, obesity, metabolic syndrome, neurological disorders, and certain cancers.4

Chemistry

The unique combination of nutrients, phytochemicals, and fiber found in strawberries appears to work synergistically to provide several health benefits. The polyphenols and vitamins in strawberries are considered to be the components primarily responsible for their antioxidant and anti-inflammatory activities, with a single serving providing more than 1 mg of polyphenols. However, the bioavailability of polyphenols has been shown to be low in vivo. Kaempferol, quercetin glycosides, cyanidin, pelargonidin, ellagic acid, and ellagitannins are among the approximately 40 phenolic compounds identified. Strawberries ranked second in total soluble phenolic content among nopal, papaya, guava, black sapote, avocado, mango, and prickly pear.3, 4 The total phenolic content and antioxidant activity of strawberry leaf extract is also very high.5 Strawberries are an important source of vitamins C (60 mg per 100 g of fresh fruit) and E, B vitamins, folate (24 mcg per 100 g of fresh fruit), carotenoids, potassium, and phytosterols, as well as the flavonoids pelargonidin, quercetin, and catechin. Other nutritional phytochemicals include vitamin A, vitamin K, manganese, iodine, magnesium, copper, iron, and phosphorus, as well as dietary fiber and fructose.3, 4 Glucose, fructose, and sucrose are the major soluble sugars found in the fruit, with glucose and fructose found in almost equal concentrations; these 3 sugars are found during all stages of ripening.2

In addition to vitamin C and ellagitannins, anthocyanins (highly pigmented polyphenolic compounds that impart the deep color in berry fruits) are among the principal bioactive metabolites contributing to the antioxidant activity of strawberries. Of the 6 common anthocyanidins found in fruits and vegetables (pelargonidin, cyanidin, delphinidin, peonidin, petunidin, and malvidin), the anthocyanin derivatives in strawberries are primarily pelargonidin based (cyanidin-3-glucoside, pelargonidin-3-glucoside [88%], pelargonidin-3-rutinoside, and pelargonidin-3-malonyl glucoside) and exhibit dose-dependent absorption.3, 6 In addition to antioxidant activity, ellagic acid and ellagitannins exhibit anticarcinogenic activity as well as inhibitory activity on angiotensin-converting enzyme. Strawberries have been reported to have higher level of free ellagic acid (1.77 mg per 100 g of fresh weight) than raspberries (0.58 mg per 100 g), pineapples (0.08 mg per 100 g), and pomegranates (1.73 mg per 100 g), but lower levels than blackberries (8.77 mg per 100 g), raspberry jam (2.25 mg per 100g), and strawberry jam (2.01 mg per 100 g).3, 7

Flavonoids are potent free radical scavengers that also provide anti-inflammatory, vasodilatory, and antiproliferative functions. One study reported flavonol and proanthocyanidin content variations depending on cultivar, with content of strawberries grown in Spain ranging from 1.5 to 3.4 mg per 100 g and 54 to 163 mg per 100 g of fresh weight, respectively; catechin or epicatechin accounted for 17% to 28% of total proanthocyanidins; quercetin and kaempferol conjugates were the main flavonol compounds identified. Fisetin has also been documented. Although low in quantity relative to other polyphenols, flavonols have a higher bioavailability. The flavonol 2,5-dimethyl-4-hydroxy-3-[2H]furanone (DMHF or furaneol) gives strawberries their characteristic aroma and pleasant taste and is often used as an industrial flavoring agent.3, 8 With respect to cranberries, blueberries, black currants, red currants, red raspberries, and blackberries, the proanthocyanidin content in strawberries is in the intermediate range (1,450 mg/kg of fresh weight).3

Phytosterols have functional similarities to cholesterol and have been shown to improve lipid parameters in clinical trials at an average dose of 2 g/day. Fresh strawberries can provide approximately 0.7 mg of total phytosterols per 6 g of strawberries, whereas freeze-dried strawberries (10% of fresh weight) were shown to provide 50 mg of phytosterols per 50 g of freeze-dried weight.3

Uses and Pharmacology

As with most natural foods, numerous factors can impact the bioactivity and bioavailability of the nutrients and phytochemicals in strawberries. For example, agricultural practices such as compost socks, compared with plastic mulch or matted rows, have been associated with higher antioxidant capacity. Whether grown under conventional or sustainable agricultural practices, frozen strawberries were observed to contain higher polyphenols than freeze-dried or air-dried strawberries, and those processed by air drying had the lowest vitamin C and polyphenol levels. Vacuum drying has been shown to be the most effective method for preserving total antioxidants, vitamin C, and color compared with freeze drying, vacuum-microwave drying, and convection drying. Processing into juice, puree, jams, or canned products, especially with conventional thermal methods that use higher temperatures, also results in lower vitamin C, polyphenol, anthocyanidin, and total phenol levels, as well as lower antioxidant activity. Fresh or frozen strawberries appear to retain the highest health and nutritional benefits, even with the minor deterioration that results after 6 days of refrigeration. However, this bioactivity does not necessarily translate equally into bioavailability.3, 9

Bioavailability can be affected by the gut microbiome, as well as by processing methods and components of the food matrix. Anthocyanin metabolism appears to undergo gastric conversion, followed by microbial metabolism in the small intestine and colon into pelargonidin, monoglucoronides, and sulfoconjugates of pelargonidin. Although in one study with healthy volunteers no difference in plasma phenolic acids was found following consumption of 300 g of fresh versus 4-day refrigerated (stored) strawberries, plasma alpha-carotene levels and urinary metabolites of pelargonidin were higher following fresh strawberry consumption. Absorption of anthocyanins was found to be negatively affected when strawberries were consumed along with fat-rich food (ie, cream) compared with fresh fruit or puree. The efficiency of colonic microbial metabolism also impacts bioavailability; urinary ellagitannins and ellagic acid were lower after strawberry consumption compared with consumption of raspberries, red wine, or walnuts.3, 9

Antihyperlipidemic effects

Clinical data

In a randomized, crossover substudy of hyperlipidemic patients (N=28) randomized to receive a 1 lb dietary strawberry daily supplement (454 g/day) or calorie-equivalent oat bran bread per 2,000 kcal/day diet for 1 month (as replacements for desserts, cakes, muffins, pastries, and cookies) following a long-term (mean duration, 2.5 years) single-phase, open-label, cholesterol-lowering dietary intervention study, no difference in blood lipids occurred between treatments compared with baseline. However, a significant reduction in oxidative damage to low-density lipoprotein (LDL) cholesterol was observed after 4 weeks of consumption of strawberries (but not of oat bran bread), reflecting a potential reduction in atherogenicity. Additionally, no change was observed for blood pressure, hematologic parameters, C-reactive protein, serum electrolytes, fasting glucose, or renal or liver function in either group.10 In contrast, a 7-week double-blind, randomized, crossover, pilot study in 31 obese subjects (body mass index [BMI] 30 to 40 kg/m2) evaluated the effect of strawberries on cardiometabolic risk factors or other health risks known to be associated with morbidity and mortality in obese individuals. All meals were provided to participants; breakfast and dinner were supervised. Exclusion criteria included vegetarianism and use of antihyperlipidemics, steroids, thyroid-regulating medications, or weight loss products. Participants consumed the equivalent of 320 g/day of strawberries in the form of a powder mixed as a milk shake, in yogurt, in cream cheese, or in a water-based sweetened beverage. Controls contained strawberry flavoring and red food coloring. Of the 31 subjects, 5 dropped out because of dislike of the provided meals and 6 for reasons unrelated to the study. Compared with the control intervention, dietary strawberry produced improvements in blood sodium and carbon dioxide (P<0.05 each), serum cholesterol (P=0.0438), small HDL particles and small HDL cholesterol (P<0.05 each), and mean LDL particle size (P<0.05). Acute-phase protein fibrinogen was increased in subjects receiving strawberry powder but remained within normal limits, and no differences in other inflammatory markers or antioxidant status were observed between the 2 dietary groups.11 Similarly, a randomized, controlled, dose-response study (N=60) evaluated the effect of freeze-dried strawberry supplement beverage (kosher, nonorganic, standardized to polyphenol content) on cardiometabolic parameters in hyperlipidemic patients with abdominal adiposity. Changes in total serum cholesterol (−33 mg/dL), LDL cholesterol (−27.5 mg/dL), and nuclear magnetic resonance–derived small LDL particles (−301 nmol/L) were significantly better over 12 weeks with administration of high-dose freeze-dried strawberry (50 g/day [25 g twice daily]) compared with low-dose freeze-dried strawberry (25 g/day [12.5 g twice daily]) (P<0.05 for each). Only high-dose strawberry supplementation produced significant improvements in total and LDL cholesterol (P<0.05) compared with controls. Reductions in the lipid oxidation biomarker malondialdehyde (MDA) were also observed with both the high and low doses of the strawberry beverage (P<0.01 and P<0.001, respectively). No differences were noted in blood pressure, anthropometrics, or measures of glycemia between the 2 groups.12 This study built on an earlier randomized controlled study (N=30) by the same author, in which dietary supplementation of 50 g/day (25 g twice daily) of strawberry beverage (equivalent to 500 g of fresh strawberries) was administered for 8 weeks to patients with clinically significant obesity (BMI greater than 35 kg/m2) and metabolic syndrome. Strawberry supplementation improved total cholesterol, LDL cholesterol, small LDL particle concentrations, and vascular cell adhesion molecule-1 (P<0.5 for all) but had no effect on features of metabolic syndrome (eg, waist circumference, blood pressure, fasting glucose) or other lipid parameters.13

Anti-inflammatory effects

Clinical data

Some anti-inflammatory activity has been reported with dietary strawberry supplementation in antitumor and cardiometabolic studies.14, 15 In a 6-month, phase 2, randomized, controlled, unblinded study investigating the effects of 2 doses of freeze-dried strawberries in adults older than 40 years (N=75) with esophageal dysplastic lesions, protein expression of inflammatory biomarkers in esophageal mucosa was reduced with 60 g/day of freeze-dried strawberry powder but not with 30 g/day.14 Similarly, in a single-blind, randomized, placebo-controlled, crossover trial (N=26) in at-risk overweight adults, the addition of a milk-based strawberry beverage made from 10 g of freeze-dried strawberry powder (equivalent to 100 g of fresh strawberries) to a single high-carbohydrate, moderate-fat test meal (bagel, margarine, cream cheese, cantaloupe, and egg) significantly improved postprandial plasma inflammation biomarkers such as high-sensitivity C-reactive protein (hs-CRP; P=0.02) and interleukin 6 (IL-6) (P<0.05).15

Antioxidant effects

Strawberries are among the most commonly consumed fruits in the United States and, along with apples, are reported to be the largest contributor to dietary cellular antioxidant activity. They have the highest oxygen radical absorbance capacity (ORAC), followed by black raspberries, blackberries, and red raspberries.3 Antioxidant activity may result from direct binding to and neutralization of free radicals, indirectly via various signaling pathways, or by cellular processes that are completely independent of antioxidant mechanisms.16

Experimental data

The effects of conventional and high-pressure processing (HPP), as well as 5 weeks of refrigeration, on antioxidant capacity, anthocyanin content, and microbial safety were assessed in strawberry-based beverages with and without milk. Antioxidant capacity was assessed by both ORAC and ferric reducing antioxidant power (FRAP) assay methods, which respectively measure the ability to directly bind to and neutralize free radicals and the ability to reduce the ferric complex. Addition of milk and processing, especially high temperature-short time (HTST) processing, significantly reduced anthocyanin and polyphenol activity. Unprocessed strawberry beverages containing milk had significantly lower antioxidant capacity (both ORAC and FRAP) than those without milk (P<0.001). Likewise, processing under HTST (but not HPP) significantly reduced antioxidant capacity in strawberry beverages compared with the unprocessed formulations (P<0.001). In contrast, HPP processing of the dairy strawberry formula significantly increased ORAC values compared with the same unprocessed formula (P<0.001). Vitamin C content was highest in the nondairy strawberry beverages (73.3 mcg/mL) versus dairy strawberry and dairy nonstrawberry beverages (49.9 and 12.6 mcg/mL, respectively). Vitamin C content in the dairy strawberry formula was significantly reduced by HTST treatment (P<0.05). Storing the beverages under refrigeration for 5 weeks also significantly reduced the ORAC values of all beverages regardless of processing method (P<0.05), with the majority of the decline occurring within the first 2 weeks. HTST processing resulted in significantly greater reductions than the HPP method in all stored beverages, as measured by both ORAC and FRAP.9

Clinical data

Smaller clinical studies (N=7 to 54) conducted in healthy volunteers demonstrated the ability of strawberry consumption to increase plasma antioxidant capacity when assayed by various methods. Studies have evaluated either the addition of a single dose of strawberries or daily supplementation added to the participant’s usual diet for up to 30 days.8, 16, 17 Following a single meal of 300 g of strawberries without added macronutrients, a significant increase in antioxidant capacity (by 7% to 9.5%) was observed when the whole plasma assay method was used but not when the traditional protein extraction assay method was used. Overall, data from a coordinated series of 5 clinical trials (N=35) indicated that consumption of certain berries, including strawberries, and fruits increased postprandial plasma antioxidant capacity, and that consumption of macronutrients without antioxidants was associated with a decline in plasma antioxidant capacity.16 In another study, a modest increase in antioxidant capacity by 20% (via lipid peroxidation protection) was documented subsequent to consumption of 250 g of thawed strawberries eaten with breakfast for 3 weeks (plain or as part of an undefined smoothie preparation). Plasma concentrations of the various anthocyanin metabolites were highly variable among the participants. Protection of DNA from oxidation was not found to change following strawberry consumption.8 In another study, consumption of 500 g of sustainably grown strawberries added to the participant’s usual diet for 30 days produced a significant decrease in the generation of reactive oxygen species by circulating phagocytes compared with baseline (by 38.2%; P<0.05). This improvement in systemic oxidative stress disappeared during the 10-day washout period and partially returned (18.7%, not statistically significant) upon reintroduction of the same dose of organically grown strawberries.17

Another study examined the effects of strawberry pulp on paraoxonase-1 (PON-1) enzyme activity and lipid levels in nonobese healthy adult subjects.18 A dose of 500 mg/day was given for 30 days, and after a 10-day washout period was followed by a second treatment course for 30 days. PON-1 activity was decreased by 5.4% after the first course (not significant) and by 11.6% (P<0.05) after the second course of treatment. Total cholesterol levels, but not other lipid levels, were transiently decreased during the first course of treatment.

Antitumor effects

Clinical data

A phase 2 randomized, controlled, unblinded study in China investigated the effects of 2 doses of freeze-dried strawberries on esophageal dysplastic lesions in adults older than 40 years (N=75) living in high-risk regions for esophageal squamous cell carcinoma. The effect of dietary strawberry consumption was measured according to histologic grade of precancerous lesions and biomarkers of cell proliferation, inflammation, and gene transcription. Strawberries sourced from California were freeze dried and lyophilized; the powder was mixed with 240 mL of water and administered at a dose of 30 or 60 g/day. Among patients receiving 60 g of strawberries, a significant decrease in histologic grade occurred in 84% (26 of 31) of patients with mild dysplasia and 60% (3 of 5) of patients with moderate dysplasia after 6 months of treatment (P<0.0001). Overall, a decrease in histological grade was observed in 80.6% of participants in the 60 g/day group, while no significant changes in precancerous growth were observed with 30 g/day. Protein expression of inflammatory biomarkers in esophageal mucosa as well as cell proliferation were also reduced in the 60 g/day group but not the 30 g/day group.14

Cardiometabolic effects

Data regarding cardiometabolic effects evaluated in studies of strawberry use in hyperlipidemia and diabetes are discussed in the respective Antihyperlipidemic and Diabetes sections.

Diabetes

In vitro data

An in vitro study evaluated the antiproliferative activity of ellagic acid and purified ellagitannins extracted from strawberries, as well as of a strawberry extract. Results suggest that the strawberry extract provided a better protective effect against hyperglycemia. In contrast to the extracted phenolics, strawberries exhibited a synergistic effect (due to the many bioactive compounds present) and high alpha-glucosidase and low alpha-amylase inhibitory activity, suggesting a role in the early management of hyperglycemia linked to type 2 diabetes.7

Clinical data

Results from randomized controlled studies on the consumption of dietary strawberries and their effects on postprandial insulin and glucose concentrations are equivocal.10, 12, 15, 19, 20 In a single-blind, randomized, placebo-controlled, crossover trial (N=26) in at-risk overweight adults, effects of strawberry antioxidants on postprandial inflammation and insulin sensitivity were documented. Exclusion criteria included use of antihyperlipidemic or anti-inflammatory medications or supplements, diabetes, atherosclerotic or other chronic inflammatory disease, and uncontrolled hypertension that would limit extrapolation of the results. Overweight or obese adult participants (mean BMI, 29 kg/m2) consumed a single test meal with a strawberry milk-based beverage made from freeze-dried strawberry powder or a placebo milk-based strawberry-flavored beverage. Addition of strawberry to the high-carbohydrate, moderate-fat test meal (bagel, margarine, cream cheese, cantaloupe, and egg) significantly improved postprandial plasma inflammation biomarkers such as hs-CRP (P=0.02) and IL-6 (P<0.05), as well as insulin concentrations (P=0.01). The strawberry beverage was equivalent to 100 g of fresh strawberries, delivering 94.7 mg of total phenols with an ORAC of 5,163 microM Trolox equivalents.15 In a follow-up study, the same study population was randomized to receive placebo or the milk-based strawberry beverage with the test meal for 6 weeks to assess the fasting and postprandial prothrombotic and proinflammatory responses to longer-term strawberry consumption. After 6 weeks, no significant differences were found in fasting glucose, insulin, hs-CRP, IL-6, IL-1beta, tumor necrosis factor (TNF)-alpha, or plasminogen activator inhibitor-1 (PAI-1) within or between groups. However, consumption of the strawberry beverage significantly attenuated meal-induced postprandial PAI-1 compared with placebo (P=0.002); this was most notable at 6 hours after the meal. Attenuation of postprandial IL-1beta and IL-6 was also observed but was not significant when corrected for baseline variability.20 In a 6-week, double-blind, randomized, controlled trial of 40 patients diagnosed with type 2 diabetes for more than 1 year, freeze-dried strawberry powder (25 g) was dissolved in water and consumed twice daily, at least 6 hours apart, as a supplement to the patients’ usual diet (equivalent to 500 g/day of fresh strawberries). A statistically significant decrease in hemoglobin A1c (HbA1c) (from 7% at baseline to 6.72%) was demonstrated with freeze-dried strawberry compared with control; this change was statistically significant between groups (P<0.5). No changes were noted in serum glucose concentrations or anthropometric indices. Also, when evaluating treatment effects on metabolic complications of type 2 diabetes, significant within-group and between-group improvements in total antioxidant status (P=0.025 and P=0.001, respectively), plasma hs-CRP (P=0.003 and P=0.02), and lipid peroxidation via MDA levels (P=0.001 and P=0.013) were observed with strawberry supplementation.19

In a randomized, crossover trial in 12 healthy volunteers (10 women), a purée of bilberries, blackcurrants, cranberries, and strawberries (150 g total; 37.5 g of each berry) with 35 g of sucrose improved plasma glucose, serum insulin, and the glycemic profile compared with a control meal. Maximum glucose concentrations were almost 30% lower after the berry meal; serum insulin levels were lower at 15 minutes and higher at 90 minutes. However, no difference was noted in area under the curve (AUC).21 Likewise, in a similar randomized, controlled, crossover study in up to 20 women, strawberries and berry purée ingested with white wheat bread significantly improved the glycemic profile compared with white bread alone (P<0.05 and P=0.005, respectively).22 A similar and significant response was observed with strawberries on postprandial insulin. Compared with rye bread alone, the berry purée improved glucose AUC at 0 to 30 minutes (P=0.026); increased the value of the glycemic profile (P=0.05); and reduced the maximum insulin increase from baseline (P=0.001) as well as insulin AUC at 30, 60, and 120 minutes (P<0.001, P<0.001, and P=0.03, respectively).

Immunomodulation

Clinical data

A 7-week, double-blind, randomized, controlled, crossover trial investigated the effects of dietary strawberries on the function of specific cell types of the innate and adaptive immune systems in obese volunteers (20 to 50 years of age; BMI of 30 to 40 kg/m2).23 Volunteers received foods containing freeze-dried strawberry powder (equivalent to 4 servings/day of frozen strawberries) or strawberry flavoring for 3 weeks, and were then crossed over to the other intervention for 3 weeks. Proliferation of CD4+ cells was decreased modestly but significantly during the strawberry phase (P=0.016), and an increase in the proliferative response of CD8+ T-cells was also observed (P=0.029). TNF-alpha production also increased in activated monocytes of participants who consumed the dietary strawberry powder. No differences were observed in IL-1beta, IL-6, IL-8, or cytokine production by T-lymphocyte subsets. Additionally, changes in gene expression for an array of genes important in modulating immune responsiveness were documented; 18 genes were upregulated and 14 genes were downregulated by dietary strawberry consumption compared with controls.

Neuronal function

Animal data

Dietary supplementation with freeze-dried strawberry and blueberry significantly improved motor performance, cognition, short-term memory, neurogenesis, and insulinlike growth factor 1 (IGF-1) in male Fisher rats (N=44). Only the blueberry diet had a significant benefit in 1 of the 5 psychomotor tests compared with controls (P<0.05). Both the strawberry (P=0.05) and the blueberry (P=0.007) groups showed improvement in cognitive performance, specifically with regards to working (ie, short-term) memory. Only rats in the strawberry diet group showed increases in the number of cells surviving in the dentate gyrus of the hippocampus compared with controls (P<0.05). IGF-1 levels increased with both berry diets (P<0.05), and levels in the strawberry group were higher than in the blueberry group (P<0.05). Although both berry groups exhibited improvements in neurocognitive function, the berries appear to have acted by different mechanisms. For example, the strawberry group was better with general balance and coordination, whereas the blueberry group was better with psychomotor coordination and vestibular integrity.24

Other uses

Extracts from the leaves of strawberries, blackcurrants, and apples were used to determine the effect of polyphenols on the erythrocyte membrane. Hemolysis, osmotic resistance, and erythrocyte shape were measured. Extracts from strawberry leaves at concentrations of 0.1 to 0.5 mg/mL did not induce hemolysis; at 0.01 mg/mL, a marked decrease in red blood cell hemolysis occurred relative to controls. The erythrocyte membrane became more resilient and less sensitive to changes in osmotic pressure. At 0.01 to 0.06 mg/mL, the generalized polarization of the membrane decreased markedly with the strawberry leaf extract, causing the greatest changes of the polar heads of lipids. Finally, the shape of the erythrocytes in the presence of the extracts was predominantly echinocytes, indicating that the phenolic compounds contained in the extracts are present in the outer lipid layer of the erythrocyte membrane.5

Dosing

Metabolism and absorption of pelargonidin-3-glucoside, the major anthocyanin in strawberries, as well as its 3 monoglucuronide metabolites, occurred in a dose-dependent manner, with maximum urinary output of anthocyanins occurring within 12 hours of consumption (greater than 50% by 4 hours and greater than 90% by 10 hours). Approximately 2% of the dose was recovered within 24 hours.6 In clinical studies, 1 g of freeze-dried strawberries was equivalent to approximately 10 g of fresh strawberries.

Antihyperlipidemic

A daily dietary strawberry supplement of 1 pound (454 g) per 2,000 kcal/day diet for 1 month has been used as a replacement for desserts, cakes, muffins, pastries, and cookies.10 In a study of hyperlipidemic adults with abdominal adiposity, 50 g/day (high dose) or 25 g/day (low dose) of freeze-dried strawberry powder beverage (kosher, nonorganic, standardized to polyphenol content) was given for 12 weeks to improve total and LDL cholesterol.12 Obese subjects (BMI 30 to 40 kg/m2) were given dietary freeze-dried strawberry powder (equivalent to 320 g/day of strawberries) mixed as a milkshake, in yogurt, in cream cheese, or as a water-based sweetened beverage.11 In clinical trials, phytosterols have been shown to improve lipid parameters at an average dose of 2 g/day. Fresh strawberries provide approximately 0.7 mg of total phytosterols per 6 g of strawberries, whereas freeze-dried strawberries (10% of fresh weight) provide 50 mg of phytosterols per 50 g of freeze-dried strawberries.3

Anti-inflammatory

60 g/day of freeze-dried strawberry powder for 6 months has been used to reduce protein expression of inflammatory biomarkers in esophageal mucosa in adults with esophageal dysplastic lesions.10 In another study, a milk-based strawberry beverage from 10 g of freeze-dried strawberry powder (equivalent to 100 g of fresh strawberries delivering 94.7 mg of total phenols, with an ORAC of 5,163 mcM Trolox equivalents) was added to a single, high-carbohydrate, moderate-fat test meal to improve postprandial plasma inflammation biomarkers in at-risk overweight adults15; the same beverage was administered for 6 weeks in a follow-up trial.20

Antioxidant

Beneficial antioxidant effects have been noted in healthy volunteers with a single meal of 300 g of strawberries16; 250 g of thawed strawberries eaten with breakfast for 3 weeks (plain or as part of an undefined smoothie preparation)8; or 500 g of sustainably grown strawberries added to usual diet for 30 days.17

Antitumor

60 g/day of freeze-dried strawberry powder for 6 months has been used in patients with mild and severe dysplastic precancerous lesions.14

Diabetes

A milk-based strawberry beverage (equivalent to 100 g of fresh strawberries delivering 94.7 mg of total phenols with an ORAC of 5,163 mcM Trolox equivalents) added to a single high-carbohydrate, moderate-fat test meal (bagel, margarine, cream cheese, cantaloupe, and egg) has been administered to improve postprandial plasma insulin concentrations in overweight and obese participants15; however, no difference was found when this beverage was given over 6 weeks.20 However, 25 g twice daily of freeze-dried strawberries (equivalent to 500 g/day of fresh strawberries) for 6 weeks reduced HbA1c from 7% to 6.72% in patients with type 2 diabetes mellitus.19

Immunomodulation

Freeze-dried strawberry powder equivalent to 4 servings/day of frozen strawberries was consumed with meals for 3 weeks to evaluate changes in innate and adaptive immune systems in obese volunteers.23

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Data from an in vitro transport study on P-glycoprotein demonstrated inconclusive results for the effect of strawberry extract on cimetidine transport across intestinal epithelial; contrary results were observed in the 2 models studied.25

Adverse Reactions

Strawberry supplementation in rats for 16 weeks did not result in negative effects on animal development.26 In clinical studies assessing adverse effects of dietary supplementation with strawberries, no adverse events occurred with 6 to 12 weeks of supplementation.12, 13, 19

A case of a local reaction to a strawberry-scented anesthetic face mask was reported in a 9-year-old girl with a known allergy to the artificially flavored strawberry drink mix Nesquik. It should be noted the mask did not contain strawberries or any ingredient related to strawberries.27

Strawberry is one of the 10 most common fruits identified in fruit allergy reports. Fruit allergies are most commonly a cross-reactivity to antibodies against homologous proteins found in plant foods and pollens, and are observed with a few rare fruits (eg, tropical fruits, berries) in susceptible individuals. Foods belonging to the Rosaceae family (eg, apple, pear, peach, strawberry, almond) most commonly cause allergic symptoms in individuals with birch pollen allergies. The strawberry Fra a 1 allergen (specifically Fra a 1.02) is a homolog of the major birch (Betula verrucosa) pollen allergen Bet v 1 (an isoflavone reductase) and is found in red ripe strawberry fruit but not in the white strawberry mutated genotype; the latter has been shown to be tolerated by strawberry-allergic individuals. The main clinical symptoms are oral allergic reactions, itching, and dermatitis; systemic reactions (eg, asthma, anaphylaxis) are rare.28, 29 A population-based survey of Mexican elementary school children documented a 0.6% (6 of 1,049) incidence of food allergy to strawberries as reported by parents, with 0.2% (2 of 1,049) experiencing an anaphylactic reaction.30

Toxicology

No data.

References

1. Liston A, Cronn R, Ashman TL. Fragaria: a genus with deep historical roots and ripe for evolutionary and ecological insights. Am J Bot. 2014;101(10):1686-1699.253266142. Hummer KE, Hancock J. Strawberry genomics: botanical history, cultivation, traditional breeding and new technologies. In: Folta KM, Gardiner SE, eds. Genetics and Genomics of Rosaceae. Vol. 7. New York, NY: Springer; 2009:413-435.3. Basu A, Nguyen A, Betts NM, Lyons TJ. Strawberry as a functional food: an evidence-based review. Crit Rev Food Sci Nutr. 2014;54(6):790-806.243450494. Giampieri F, Forbes-Hernandez TY, Gasparrini M, et al. Strawberry as a health promoter: an evidence based review. Food Funct. 2015;6(5):1386-1398.258031915. Cyboran S, Oszmiański J, Kleszczyńska H. Interaction between plant polyphenols and the erythrocyte membrane. Cell Mol Biol Lett. 2012;17(1):77-88.221610786. Carkeet C, Clevidence BA, Novotny JA. Anthocyanin excretion by humans increases linearly with increasing strawberry dose. J Nutr. 2008;138(5):897-902.184245987. Pinto Mda S, de Carvalho JE, Lajolo FM, Genovese MI, Shetty K. Evaluation of antiproliferative, anti-type 2 diabetes, and antihypertension potentials of ellagitannins from strawberries (Fragaria × ananassa Duch.) using in vitro models. J Med Food. 2010;13(5):1027-1035.206262548. Henning SM, Seeram NP, Zhang Y, et al. Strawberry consumption is associated with increased antioxidant capacity in serum. J Med Food. 2010;13(1):116-122.201364449. Tadapaneni RK, Banaszewski K, Patazca E, et al. Effect of high-pressure processing and milk on the anthocyanin composition and antioxidant capacity of strawberry-based beverages. J Agric Food Chem. 2012;60(23):5795-5802.2222458810. Jenkins DJ, Nguyen TH, Kendall CW, et al. The effect of strawberries in a cholesterol-lowering dietary portfolio. Metabolism. 2008;57(12):1636-1644.1901328511. Zunino SJ, Parelman MA, Freytag TL, et al. Effects of dietary strawberry powder on blood lipids and inflammatory markers in obese human subjects. Br J Nutr. 2012;108(5):900-909.2206801612. Basu A, Betts NM, Nguyen A, Newman ED, Fu D, Lyons TJ. Freeze-dried strawberries lower serum cholesterol and lipid peroxidation in adults with abdominal adiposity and elevated serum lipids. J Nutr. 2014;144(6):830-837.2467097013. Basu A, Fu DX, Wilkinson M, et al. Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome. Nutr Res. 2010;30(7):462-469.2079747814. Chen T, Yan F, Qian J, et al. Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus. Cancer Prev Res (Phila). 2012;5(1):41-50.2213504815. Edirisinghe I, Banaszewski K, Cappozzo J, et al. Strawberry anthocyanin and its association with postprandial inflammation and insulin. Br J Nutr. 2011;106(6):913-922.2173685316. Prior RL, Gu L, Wu X, et al. Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status. J Am Coll Nutr. 2007;26(2):170-181.1753612917. Bialasiewicz P, Prymont-Przyminska A, Zwolinska A, et al. Addition of strawberries to the usual diet decreases resting chemiluminescence of fasting blood in healthy subjects-possible health-promoting effect of these fruits consumption. J Am Coll Nutr. 2014;33(4):274-287.2491205318. Zasowska-Nowak A, Nowak PJ, Bialasiewicz P, et al. Strawberries added to the usual diet suppress fasting plasma paraoxonase activity and have a weak transient decreasing effect on cholesterol levels in healthy nonobese subjects. J Am Coll Nutr. 2016;35(5):422-435.2693467119. Moazen S, Amani R, Homayouni Rad A, Shahbazian H, Ahmadi K, Taha Jalali M. Effects of freeze-dried strawberry supplementation on metabolic biomarkers of atherosclerosis in subjects with type 2 diabetes: a randomized double-blind controlled trial. Ann Nutr Metab. 2013;63(3):256-264.2433486820. Ellis CL, Edirisinghe I, Kappagoda T, Burton-Freeman B. Attenuation of meal-induced inflammatory and thrombotic responses in overweight men and women after 6-week daily strawberry (Fragaria) intake. A randomized placebo-controlled trial. J Atheroscler Thromb. 2011;18(4):318-327.2124265221. Törrönen R, Sarkkinen E, Niskanen T, Tapola N, Kilpi K, Niskanen L. Postprandial glucose, insulin and glucagon-like peptide 1 responses to sucrose ingested with berries in healthy subjects. Br J Nutr. 2012;107(10):1445-1451.2192983822. Törrönen R, Kolehmainen M, Sarkkinen E, Poutanen K, Mykkänen H, Niskanen L. Berries reduce postprandial insulin responses to wheat and rye breads in healthy women. J Nutr. 2013;143(4):430-436.2336510823. Zunino SJ, Storms DH, Freytag TL, et al. Dietary strawberries increase the proliferative response of CD3/CD28-activated CD8⁺ T cells and the production of TNF-α in lipopolysaccharide-stimulated monocytes from obese human subjects. Br J Nutr. 2013;110(11):2011-2019.2359726724. Shukitt-Hale B, Bielinski DF, Lau FC, Willis LM, Carey AN, Joseph JA. The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Br J Nutr. 2015;114(10):1542-1549.2639203725. Tarirai C, Viljoen AM, Hamman JH. Effects of dietary fruits, vegetables and a herbal tea on the in vitro transport of cimetidine: comparing the Caco-2 model with porcine jejunum tissue. Pharm Biol. 2012;50(2):254-263.2208527826. Diamanti J, Mezzetti B, Giampieri F, et al. Doxorubicin-induced oxidative stress in rats is efficiently counteracted by dietary anthocyanin differently enriched strawberry (Fragaria × ananassa Duch.). J Agric Food Chem. 2014;62(18):3935-3943.2458002527. von Ungern-Sternberg BS, Hegarty M. Local reaction to a scented face mask in a child. Paediatr Anaesth. 2012;22(11):1141.2563169928. Franz-Oberdorf K, Eberlein B, Edelmann K, et al. Fra a 1.02 Is the Most Potent Isoform of the Bet v 1-like Allergen in Strawberry Fruit. J Agric Food Chem. 2016;64(18):3688-3696.2708670729. Hassan AK, Venkatesh YP. An overview of fruit allergy and the causative allergens [published correction appears in Eur Ann Allergy Clin Immunol. 2016;48(1):31]. Eur Ann Allergy Clin Immunol. 2015;47(6):180-187.2654933430. Ontiveros N, Valdez-Meza EE, Vergara-Jiménez MJ, Canizalez-Román A, Borzutzky A, Cabrera-Chávez F. Parent-reported prevalence of food allergy in Mexican schoolchildren: A population-based study. Allergol Immunopathol (Madr). 2016;44(6):563-570.27475776

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