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American Journal of Biomedical Sciences

ISSN: 1937-9080

Diet Antioxidant Capacity: Relationships to Oxidative Stress and Health
Ronald L. Prior1* , Xianli Wu 2
1 2

214 Lakeshore Drive, Searcy, AR 72143, USA Hershey Center for Health and Nutrition, The Hershey Company, 1025 Reese Avenue, Hershey, PA 17033, USA * Corresponding author: Ronald L. Prior 214 Lakeshore Drive Searcy, AR 72143 USA Email: Received: 30 January 2013; | Revised: 25 February 2013; | Accepted: 28 March 2013

Abstract This review will discuss some of the antioxidant assays and biomarkers/measurements used to assess the effect of dietary components on ameliorating in vivo oxidative stress. Although the development of dietary antioxidants has become a major component of the dietary supplement market, this review will focus on foods (primarily fruits and vegetables) and their impact on biomarkers of oxidative stress and the ultimate appearance of disease states. Data is reviewed demonstrating the importance of consumption of dietary antioxidants along with meals to prevent postprandial oxidative stress. Epidemiology studies have demonstrated the relationships between dietary antioxidant intake in the form of polyphenolic type compounds and health outcomes. However, additional research is needed in order to clearly define the mechanism(s) of action of the polyphenolics and whether their effects are direct or indirect in nature. Keywords: Antioxidant, Oxidative stress, Diet. Introduction All animals need O2 for production of energy in mitochondria [1]. When cells utilize oxygen to generate energy, free radicals are created as a consequence of ATP (adenosine triphosphate) production by mitochondria. A free radical is any species containing an unpaired electron. With an unpaired electron in its atomic orbital, the free radical is highly reactive. There are many types of free radicals and non-radical reactive species in living systems; nonetheless, reactive oxygen
Am. J. Biomed. Sci. 2013, 5(2), 126-139; doi: 10.5099/aj130200126

species (ROS) are the primary reactive species in the human body. When the production of ROS overwhelms antioxidant defenses provided by antioxidants and anti-oxidative enzymes, a status called “oxidative stress” occurs. Oxidative stress leads to cellular damage and may be a causative factor or lead to progression of chronic degenerative diseases, such as cardiovascular disease, cancer and Alzheimer’s disease. Nutrient antioxidants (i.e. vitamin C, vitamin E, carotenoids, etc) have defined levels in the diet which are necessary to prevent specific
© 2013 by NWPII. All rights reserved.


To assess the effectiveness of dietary antioxidants in vivo. researchers have traditionally used a number of markers of oxidative stress and in the measurements of antioxidant defense including antioxidant enzymes such as superoxide dismutases (SOD). 5(2). For instance. Measures of antioxidant capacity have been developed to assess total antioxidants in fruits and vegetables and other dietary components and to provide another biomarker of oxidative stress in the form of plasma and tissue antioxidant capacity [3 4]. in which antioxidant and substrate compete for thermally generated peroxyl radicals through the decomposition of azo compounds. glutathione peroxidases (GPx) and catalase (CAT) as well as molecules such a albumin. in biological systems glutathione (GSH) is a major nonenzymatic antioxidant involved in the maintenance of redox balance which may ameliorate cellular oxidative damage. bilirubin and uric acid. but whether they have any direct in vivo antioxidant effects has been a topic of much debate. 3) total radical Am. 2013. this is not possible due to the very different chemistries. It has been a desire by many to have a single conversion factor that would relate different antioxidant capacity assays. measurements of © 2013 by NWPII. However. malondialdehyde and isoprostanes from lipids and 8-hydroxy-2'-deoxyguanosine (8OHdG) from DNA. ET-based assays include: 1) the total phenols assay by Folin-Ciocalteu reagent (FCR).5099/aj130200126 trapping antioxidant parameter (TRAP). Thus.deficiencies leading to disease states. 4) "total antioxidant potential" assay using a Cu(II) complex as an oxidant. In addition to possible direct effects. which is the most common radical found in biological systems. ORAC is considered particularly biologically relevant in that it uses the peroxyl radical. ET-based assays measure the capacity of an antioxidant to prevent the reduction of an oxidant. other in vivo biomarkers have been used to assess in vivo oxidative status and the effectiveness of dietary antioxidants. Thus. redox imbalance causes the activation of redox-sensitive transcription factors that lead to inflammation [2]. All rights reserved. 2) oxygen radical absorbance capacity (ORAC). and crocin bleaching assays. At the cellular and molecular levels. doi: 10. including atherosclerosis and diabetes. that show antioxidant effects in vitro. Among them. enhanced oxidative stress due to uncontrolled reactive oxygen species is a major factor in both acute and chronic inflammation and inflammatory related diseases. Although the antioxidant capacity assays can be useful for assessing antioxidant capacity of foods and also can be used for plasma and tissues. However. which changes color when reduced. there are another class of compounds found in fruits and vegetables. The degree of color change is correlated with the sample's antioxidant concentrations. recently. dietary flavonoids may also have indirect antioxidant effects by stimulating in vivo antioxidant systems which may prevent or relieve oxidative stress. different free radicals involved and reaction mechanisms of the different assays with different antioxidant compounds. 3) ferric ion reducing antioxidant power (FRAP). Assays of this type include: 1) inhibition of induced low-density lipoprotein autoxidation. The majority of HAT-based assays apply a competitive reaction scheme. The most commonly used biomarkers include carbonylated proteins. it must be realized that these are in vitro ‘test tube’ assays and do not necessarily take into account what happens to the dietary antioxidants during absorption and metabolism. commonly known as polyphenols. 127 . The total phenols assay by FCR has been used to quantify an antioxidant's reducing capacity and the ORAC assay to quantify peroxyl radical scavenging capacity was used to establish a dataset of antioxidant capacity of fruits and vegetables [6-9]. These antioxidant capacity assays can be classified into two types based on their reactions with free radicals: assays based on hydrogen atom transfer (HAT) reactions and assays based on electron transfer (ET) [5]. In addition. 2) Trolox equivalence antioxidant capacity (TEAC). Biomed. and 5) the diphenyl-1-picrylhydrazyl (DPPH) assay. Sci. These biomarkers are usually the stable oxidized products of biological macromolecules. J. Various antioxidant capacity assays have been used to assess antioxidant capacity of biological samples such as plasma and tissues in animal and human clinical studies. 126-139.

GPx and CAT) as well as non-enzyme antioxidants (i. changes in plasma antioxidant capacity (AOC).9 mmole TE of AOC. In two studies with blueberry or grape.5099/aj130200126 There is increasing evidence that oxidative stress during the immediate postprandial state may be an important contributing factor to chronic diseases. All rights reserved.e. plasma ORAC. measured by a quantitative colorimetric assay kit. dried plum. Sci. Multiple sclerosis. The role of flavonoids and other phenolic compounds in protecting health and lowering disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest. the results from the postprandial state in short term studies cannot necessarily be extrapolated to long term disease development and outcome with certainty.6 mmole Trolox Equivalents (TE) of AOC. is characterized by loss of myelin. vitamin E and ubiquinol) are also widely used to evaluate the in vivo redox status [10]. CAT and GPx levels were significantly decreased in macrosomic as compared to control newborns [14].e. because different biomarkers were utilized. Oxidative stress and abnormalities in the oxidative defense system may occur in newborn infants. decreased from the postprandial baseline AOC measurement. The implication of oxidative stress in the etiology of chronic and degenerative diseases suggests that antioxidants. 126-139. In a crosssectional study included 33 patients with multiple sclerosis and 24 age and sex matched control subjects. 39.5 mmol TE) increased plasma lipophilic-AOC but not hydrophilic-AOC. 5(2).antioxidant defenses such as antioxidant enzymes (i. Thus. © 2013 by NWPII. Blood samples collected before and after the meal were analyzed for plasma AOC. kiwifruit and strawberry) were studied in 5 clinical trials. 128 . respectively] increased plasma hydrophilic AOC AUC. as determined using ORAC. cherry. All patients had definite diagnostic categories (Poser criteria) for multiple sclerosis. vitamin E. SOD. dried plum juice. The plasma AOC in the control groups receiving no dietary antioxidant source. The results showed that oxidative stress plays an important role in pathogenesis of multiple sclerosis and suggests that dietary antioxidants may be important in the therapy of multiple sclerosis patients [15].5 and 39. and it was also believed to play a major role in the aging process [11-13]. Antioxidants and Disease Excess ROS can damage cellular lipids. such studies can provide insight into dietary components that impact oxidative stress and antioxidant status. Excessive weight could be a potential factor contributing to decreased antioxidant capacity and increased oxidative stress in newborns which may lead to abnormalities of the humoral immune defense systems [14]. following consumption of a single meal of berries/fruits (blueberry. proteins or DNA to impair their normal function. both endogenously and exogenously. albumin. oxidative stress has been implicated in the etiology of many chronic and degenerative diseases. grape. Lipophilic AOC increased following a meal of blueberry containing 12. a chronic inflammatory disease of the central nervous system. However. was ~30% lower in the multiple sclerosis group of patients compared to the control group Am. In early studies by Prior and coworkers [3]. Consumption of blueberry in 2 studies and of a mixed dried grape powder in another study [12. glutathione. fat. 2013. In a study of 30 macrosomic and 30 sexmatched control newborns. evaluation of any single biomarker/measurement or even a few may not truly reflect the overall in vivo antioxidant status. are necessary to protect cellular components from oxidative damage. of subjects. in which additional macronutrients were added. SOD. Although. protein) were included in the control and treatment meals. doi: 10. Biomed. Antioxidants Stress and Postprandial Oxidative Oxidative Stress. additional macronutrients (carbohydrate. mean serum total antioxidant capacity. the fatty tissue that surrounds and protects nerve fibers allowing them to conduct electrical impulses. Consumption of 280 g of cherries (4.9 and 8. J.5. This may be one factor leading to seemingly differing conclusions from various antioxidant research studies.

contrary to previous studies attributing the protective postprandial effect to fructose and ascorbate. flavonoids are poorly absorbed which has been interpreted that flavonoids may not directly increase serum antioxidant levels. Urolithin A. carbohydrates or the amount of energy consumed in the meal may alter the response. Blacker et al [20] found that consumption of a much lower quantity of blueberries than tested previously reduced postprandial oxidation when consumed with a typical high-carbohydrate. In another study [18]. These results showed the importance of distinguishing between the in vitro and in vivo antioxidant activities of dietary anthocyanins in relation to human health [21]. Serum ORAC and serum lipoprotein oxidation and serum ascorbate. doi: 10. Other investigators have observed increased oxidative stress in response to an oral glucose load [16]. is thought not to be responsible for the plasma antioxidant changes following strawberry consumption. Two theories have been proposed to explain how high fruit intake might increase serum antioxidant capacity. Plasma antioxidant capacity increased following consumption of 500 mL of cranberry juice which could largely be accounted for by an increase in vitamin C rather than phenolics. This compound was found to be the more significant contributor to increased serum antioxidant capacity after apple consumption. Changes in serum ascorbate. Similarly. Thus the fructosedependent hyperuremic effect. urate and glucose were not significantly different among the groups. This data demonstrated that the postprandial increase in serum antioxidant capacity is not attributable to the fructose or ascorbate content of blueberries. Lotito and Frei [17] found that higher fructose content of fruit causes an increase in serum levels of uric acid. a low blueberry dose (35 g) and a control (ascorbic acid and sugar content matching that of the high blueberry dose). 2013. produced significantly elevated plasma ORAC values. vitamin C. 129 . 126-139. phenolic compounds from oranges contributed directly to the postprandial oxidative protection in serum. 5(2). In a recent study [22]. Differences in amount and components absorbed from different foods may account for some of the lack of a direct correlation between ORAC intake and plasma antioxidant capacity. Biomed. which increased plasma antioxidant capacity. © 2013 by NWPII. This also may explain the lack of an effect on antioxidant status of a phenolic-rich (primarily anthocyanins) and vitamin C-low blueberry juice [19]. Generally. which is a major colonic microflora metabolite produced by rats and humans after consumption of ellagitannins. In this study. Sci. Another important issue is the metabolites of dietary antioxidants that are present in the circulation and the tissues. rather than the phenolic compounds.5099/aj130200126 Treatments consisted of a high blueberry dose (75 g). observed after the intake of non-berry fruits [17]. especially the catabolites generated by gut microflora from native dietary compounds. participants received each of the three treatments over 3 weeks in a cross-over design. Serum lipoprotein oxidation lag time showed a significant trend towards protection over the 3 h for both blueberry doses. Factors such as phytochemical profile of the food. ascorbate was suggested to be of more significance than phenolic compounds or urate in increasing postprandial serum antioxidant capacity when consuming only strawberries.indicating development of postprandial oxidative stress conditions. urate and glucose were measured at fasting. Cranberry juice consumption (750 mL/day for 2 weeks) did not alter blood or cellular antioxidant status or several biomarkers of lipid status pertinent to heart disease. Am. cranberry juice had no effect on basal or induced oxidative DNA damage. The mean serum ORAC was significantly higher in the 75 g blueberry group than in the control group during the first 2 h postprandially. Blacker et al [20] concluded that it was likely that the effects observed with blueberries are due to the phenolic compounds acting directly or indirectly. All rights reserved. However. the quantity of antioxidants consumed (mmol TE) in the different studies was not directly related to changes in plasma antioxidant status. to bring about the decreased postprandial oxidative stress. low-fat breakfast. However. Some metabolites. J. 2 and 3 h after treatment consumption. may be absorbed at a fairly high concentration and show comparable or even more potent antioxidant activities than their precursors. and at 1. in another study.

5 servings/day) during the previous year [28]. Sci.. regular consumption of polyphenol-rich foods. 11. However. one cannot necessarily translate increased plasma antioxidant capacity into a potential decreased risk of chronic degenerative disease. All rights reserved. indicating that the association of fruit and vegetable intake with TAP was not solely because of the presence of these well documented antioxidant vitamins [26]. However. Significant antiinflammatory effects were also observed. Relative to baseline levels. Wang and coworkers [31]. 2013. attempted to determine if plasma antioxidant capacity could effectively predict dietary intake of antioxidants and plasma antioxidant status. they may counterbalance the negative effects of the high fat/high carbohydrate diets [24]. Biomed. measured as ORAC. antioxidant capacity measured by FRAP was correlated only with uric acid. βcryptoxanthin and uric acid. Plasma antioxidant capacity was determined by vitamin C equivalent antioxidant capacity (VCEAC). plasma ORAC in these subjects was significantly increased by consuming 10 servings of fruit and vegetables per day for 10 days or by consuming 10 servings of fruits and vegetables plus 2 servings of broccoli per day. as well as with plasma total phenolics. without further long term clinical studies. Am. Seven-day food records and 12-h fasting blood samples were collected from 40 subjects for dietary and plasma antioxidant assessments. FRAP and ORAC assays. After multivariate adjustment. plasma antioxidant capacity determined by VCEAC was positively associated with dietary intakes of γ-tocopherol. 130 . These observations point out the importance of considering the flavonoid and/or its metabolites and the extent by which it might be conjugated in the absorption process as factors involved in whether an antioxidant response is observed in the blood or other tissues. Increasing numbers of studies have reported that an increase in plasma antioxidant capacity is associated with increased intake of fruits and vegetables which are rich in antioxidants [25-27]. and when they are consumed with high fat and carbohydrate 'prooxidant and pro-inflammatory' meals. was positively associated with intake of fruit and vegetables. 6. such as oxidative stress and inflammation. β-carotene. anthocyanins. Plasma antioxidant capacity determined by VCEAC and ORAC had positive correlation with plasma uric acid and total phenolics. which is a variation of the ORAC method that measures the ability of both hydrophilic and lipophilic antioxidants to quench radicals and their interactions in plasma/serum [26]. flavones. Total antioxidant performance (TAP) [29 30]. using three different antioxidant capacity assays. 5(2). The association remained after adjustment for dietary intake of β-carotene and vitamin C. 36 healthy nonsmokers resided in a metabolic research unit and consumed 2 sets of controlled diets and fasting plasma antioxidant capacity.which was associated with high plasma levels of the unconjugated form of urolithin A at 1 hour after oral administration [23]. appears to be a prudent strategy to maintain oxidative balance and health [24]. proanthocyanidins and dietary antioxidant capacity. Given the content and availability of fat and carbohydrate in the Western diet. Biomarkers/measurements Of Stress and Dietary Antioxidants Oxidative Plasma/serum measures of antioxidant capacity have been useful in the short-term postprandial studies and also in longer term diet intake studies in assessing antioxidant status and oxidative stress. doi: 10. The collected data suggested that consuming polyphenol-rich fruits increases the antioxidant capacity of the blood.5099/aj130200126 and 16 of the study. In a study by Cao et al. 126-139. J. and α-tocopherol concentrations were determined on days 1. glycemia/insulinemia and associated events. Fasting baseline plasma ORAC was significantly correlated with estimated daily intake of total antioxidants from fruit and vegetables (ave. particularly in conjunction with meals. The authors concluded that plasma antioxidant capacity measured by VCEAC reflects both dietary and plasma antioxidants and represents more closely © 2013 by NWPII. α-tocopherol. Burton-Freeman [24] reviewed the literature on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipemia. This increase in ORAC could not be explained by any increase in the plasma α-tocopherol concentration [28].

Sci. The effect of coffee consumption for a period of four weeks on antioxidant capacity and lipid peroxidation in 20 healthy volunteers was studied by Correa and coworkers (17).75% in erythrocyte superoxide dismutase. Plasma total antioxidant capacity (total and perchloric acid (PCA) protein-precipitated Am. 2013.the plasma antioxidant levels than ORAC and FRAP [31]. A significant progressive increase in fasting plasma TAC and in serum vitamin C concentrations were observed during a 16 day period of consumption of 500 g/d of strawberry in a pilot study of 16 subjects. doi: 10. Orchidectomy depressed plasma antioxidant capacity and superoxide dismutase activity.62% in erythrocyte GPx. 61% female) was associated with improved multiple markers of inflammatory and oxidant status. Two fasting blood samples were collected separated by 12 weeks. Coffee had antioxidant effects. which may have been due to both chlorogenic acids and Maillard reaction products present in coffee. Biomed. In a rat model. pro-inflammatory cytokines IL-6 and TNF-α were significantly lower across categories of increasing fruit and vegetable intakes. 13% in CAT. and 49 . These findings support current guidelines calling for increased fruit and vegetable consumption for improving antioxidant status and lowering inflammation in the prevention of chronic diseases [33]. sham-control and orchidectomized 1 year old male rats were given 27% cranberry juice or 45% cranberry juice. providing some evidence that oxidative stress may mediate reported effects of glycemic index and hyperglycemia on health [16]. No significant alterations in lipid peroxidation biomarkers (oxidized LDL and 8-epi-prostaglandin (F2α)) were observed. In analyses controlling for other important dietary and lifestyle factors. Antioxidant enzyme activities (CAT and SOD) increased significantly after strawberry extract intake and a concomitant decrease in gastric lipid peroxidation was found after 10 days. 52 . Oxidative stress and hypogonadism have been found to link to the increased incidence of cardiovascular disease in males. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity to promote the action of antioxidant enzymes [35]. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious effect. This data provides an illustration of the need to measure multiple oxidative stress biomarkers that may be important in protecting biological systems and reducing the risk of diseases related to oxidative stress [34]. Compared with baseline. while plasma FRAP and ORAC were significantly higher and F(2)isoprostanes were significantly lower. 126-139. These changes in antioxidant capacity occurred before changes in other risk factors for cardiovascular disease and diabetes. elevated nitrate + nitrite and malondialdehyde in plasma. J.26% in plasma total antioxidant status. there are studies using animal models of the effects of dietary components on oxidative stress. 131 . Enhanced resistance of erythrocytes to hemolysis in vitro was also observed with strawberry consumption [32]. cranberry juice consumption increased plasma antioxidant capacity and superoxide dismutase activity and reduced nitrate + nitrite and malondialdehyde concentrations in orchidectomized rats. age 18-85 years. The strawberry extracts provided a rich source of anthocyanins and antioxidant capacity.5099/aj130200126 plasma oxygen radical absorbance capacity (ORAC) assay) has been shown to be increased within 1 week on a low glycemic index diet in obese male subjects. subjects consuming coffee had an increase of 21 . Root et al [33] studied whether an increase in combined self-reported fruit and vegetable intake over a 12 week period in a community setting (N = 1000. 5(2). Strawberry extracts (3 different cultivars) were protective against ethanol-induced gastric mucosa damage in an in vivo rat experimental model [35]. All rights reserved. and increased © 2013 by NWPII. At 120 days after initiation of the study. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Animal Studies of Dietary Antioxidants and Health Status Although not exhaustive in terms of literature available.

the increase of at least 2 servings each of fruits and vegetables could result in an increase of more than 3000 µmole TE per day in total ORAC [3. adherence to a Mediterraneantype diet. Furthermore. berry and vegetable intake was associated with reduced risk of mortality in middle-aged Finnish men [41]. J. 6]. 61% female). suggesting that diets that are rich in plant-derived foods can promote longevity. 126-139. The protective effect of cranberry juice from oxidative damage may be mediated by a decrease in nitrate + nitrite and dose-dependent decrease in peroxidation [36]. Sci. However. The intervention with the Mediterranean diet was associated with higher levels of plasma antioxidant capacity. Serum from blueberry fed ApoE-/. Red onion fed as peel. Blueberries contain a high level of polyphenols and exhibit strong antioxidant and potential anti-inflammatory effects [6]. 5(2). 132 . suggesting that red onion may be able to reduce oxidative stress in rats [37]. ApoE-/mice fed 1% freeze-dried blueberry powder in the diet developed significantly fewer aortic lesions [38]. Clinical and Epidemiology Studies: Dietary Antioxidant and Health Outcomes Increasing numbers of studies have reported that an increase in plasma antioxidant capacity is associated with increased intake of fruits and vegetables which are rich in antioxidants [25-27]. on plasma TAC in subjects with high cardiovascular risk was studied. In a community study (N = 1000. F2isoprostanes were significantly lower across categories of fruit and vegetable intakes [33].5099/aj130200126 was shown to increase total dietary antioxidant intake and plasma total antioxidant capacity (ORAC) in this patient population [42]. Biomed. Am. parallel dietary intervention study of ninety subjects with abdominal obesity (46 in intervention group. In subsequent studies. While data were not available on dietary antioxidant intake. All rights reserved. The expression of class B scavenger receptor CD36 was reduced by 40% in the aorta from apoE-/ mice fed blueberry for 20 weeks [39]. In another study [44]. In a 2-month randomized. markers of inflammation (IL-6 and TNF-α) were significantly lower and antioxidant status (plasma FRAP and ORAC) were significantly higher across categories of increasing fruit and vegetable intakes. doi: 10. was shown to enhance antioxidant defense mechanisms through the induction of plasma SOD and GPx activities and to inhibit liver lipid peroxidation. Experimental studies suggest that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke. the influence of a Mediterranean dietary pattern. In a randomized dietary trial (PREDIMED trial). age 18-85 years. higher dietary antioxidant intakes (ORAC) had favorable effects on metabolic disorders and also in preventing subsequent weight and abdominal fat gain during a 3-year follow-up in 1938 subjects from the Tehran Lipid and Glucose Study [44]. a negative relation of dietary antioxidant indices with inflammatory markers was observed. rich in virgin olive oil. other potential mechanisms for the anti-atherotic effects of blueberry were studied using a real-time quantitative RT-PCR array with multiple antioxidant/inflammation related genes. or peel plus flesh at 5% of the diet and fed for 4 weeks to rats. These authors proposed an adiponectin-mediated route through which antioxidant-rich foods exert beneficial effects against inflammation and cardiovascular diseases [45]. A high fruit. 44 in control group).mice was also shown to inhibit signaling pathways leading to the formation of TNF-α and IL-6 [40]. Increased plasma TAC was also related to a reduction in body weight after 3 years [43].triglyceride and cholesterol values in liver and in plasma. Consuming a diet with a high total antioxidant capacity has been related to reduced inflammation and increased circulating antioxidants in crosssectional and randomized intervention studies © 2013 by NWPII. with emphasis on an increase in foods rich in antioxidants and close dietetic supervision. some of the antioxidant enzymes were up-regulated by blueberry feeding. 2013. apparently healthy adults from the ATTICA study [310 men (40±11 years) and 222 women (38±12 years)]. Detopoulou and coworkers [45] demonstrated a positive association between dietary antioxidant capacity and adiponectin concentration in free-living.

higher antioxidant intake (measured by ORAC) as estimated from a food frequency questionnaire. Dietary intake was ascertained using a food-frequency questionnaire. a stronger inverse association with dietary TAC was observed [46]. total antioxidant capacity intake assessed through the FRAP assay was not associated with colorectal cancer [52] In the EPIC cohort. particularly the lipophilic component. increasing the total phenolic consumption as reflected in ORAC intake may decrease endometrial cancer risk [50]. Total antioxidant capacity intake in the diet was negatively associated with hypertension in type 2 diabetic patients [47] in a cross-sectional study of 506 type 2 diabetic patients. Endometrial cancer risk was studied in a population-based case-control study in New Jersey. Sci. In the Health Professionals Follow-Up Study. doi: 10. The total radical-trapping antioxidant potential (TRAP) of different plant foods was used to convert food frequency intake into antioxidant potential. particularly in premenopausal women who have never smoked [54] based upon © 2013 by NWPII. a diet rich in total antioxidant capacity was associated with a reduction in risk for all types of stroke. An inverse association between selenium consumption from food sources and ovarian cancer risk was observed. In a study of the relation between dietary total antioxidant capacity and risk of ischemic and hemorrhagic stroke in 41. 133 . however. Subjects who had never-smoked with the highest antioxidant intake had the lowest risk of cancer. which utilized the FRAP assay to assess antioxidant capacity. The odds ratios of both systolic (>140 mm Hg) and diastolic blood pressure (>90 mm Hg) decreased across increasing quartiles of total dietary ORAC intake [47]. while there was little evidence of an association with total antioxidant capacity or any of the other individual antioxidants. There was also no strong evidence for an association with intake of any of the individual antioxidants. In a large population-based case-control designed study. data were collected through face-to-face interviews with 505 newly diagnosed gastric adenocarcinoma patients and 1116 control subjects to assess dietary habits 20 years before interview. based on the FRAP and TRAP assays. [48].007 frequency-matched controls. 5(2). however. total antioxidant intake. There was no association for total antioxidant intake based on the AFD. Dietary TAC may have a favorable role in respiratory health.5099/aj130200126 for smoking. the inverse relationship between TRAP values displayed a clearer dose-response pattern. but when only ischemic stroke cases were considered. Additional research is needed to confirm these findings [51]. All rights reserved. including 417 cases and 395 controls [50]. A small number of epidemiology studies have been published recently in which dietary intake of antioxidant capacity was related to outcomes of some cancers. Biomed. Using the ORAC database.620 men and women not previously diagnosed with stroke or myocardial infarction. In a clinic-based study of 603 incident cases and 1. was associated with a lower non-Hodgkin lymphoma risk after accounting for other antioxidant nutrients and vegetable intake [49]. 2013. Controlling Am. aged 28-75 years in Tehran. after adjusting for major covariates. and total antioxidant capacity intake was estimated using the USDA ORAC database and the University of Oslo's Antioxidant Food Database (AFD) and FFQ-derived estimates of intake. decreased risks of endometrial cancer was observed for the highest tertile of total phenolic intake compared with the lowest tertile. Gastric cancer risk in groups exposed to higher levels of oxidative stress (smoking and Helicobacter pylori infection) was also examined. Intake of antioxidant equivalents expressed as TRAP values was inversely associated with the risk of both cardia and distal gastric cancer. was associated with a reduction in gastric cancer risk [53]. a high intake of vitamin E may be positively associated to the risk of brain hemorrhagic events. One of the first studies using data from long term epidemiology studies to relate dietary antioxidant intake and oxidative stress-related carcinogenesis was by Serafini and coworkers [48]. 126-139.[46]. J. More focused investigations are needed on how antioxidants may play a role in reducing the risk of cerebral infarction but not hemorrhagic stroke. Total antioxidants may play a role in reducing the risk of cerebral infarction but not hemorrhagic stroke. which was only marginally significant.

10. Using the Singapore Chinese Health Study with more than 63. All rights reserved.779. 9]. In another large epidemiological study of ORAC intake from Sweden.a healthy Italian population using FRAP as a measure of TAC and the European Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment.3 years. intake of hydrophilic ORAC from fruits and vegetables was calculated to be 3827 and 1810 units.502. hydrophilic ORAC intake was calculated to be 5558 units/ day/person. 2013.000 women and men aged 45-74 yrs. Based on data on quantities of foods consumed per day from the USDA’s Continuing Survey of Food Intakes by Individuals (1994-1996.214 units or more of ORAC per day [58]. Stratified analysis showed that this relationship between dietary TAC and pulmonary function only occurred in women who were premenopausal/never smokers. the observed effect of higher FRAP intake was an increased forced expiratory volume equivalent to an improvement in pulmonary age of 3. and 18. The estimated average hydrophilic ORAC value for "typical vegetables" consumed in Japan was 594. 2 days). those in the lowest quartile of dietary ORAC (7. 126-139. based upon data from a food-frequency questionnaire. In women from this cohort with a cardiovascular disease-free history. However. 836312518. in data recalculated from an earlier study [28] using the newer food data with the latest ORAC analytical method. 5(2). respectively. C. respectively for each of the quintiles. Dietary Intake of Antioxidants Measured as ORAC Value Sufficient research data to establish definite reference dietary intakes (RDI). ORAC intakes from food frequency questionnaires based upon the previous year was 4360 units of ORAC per day (5 servings fruits and vegetables per day). ORAC intakes were somewhat lower than might be expected because the diets did not contain any of the berries and fruits that are appreciably higher in ORAC [28]. respectively for a total intake of 5636 units per day [8. The hydrophilic ORAC content of 23 vegetables commonly consumed in Japan was assessed to estimate the dietary intake of antioxidants in Japan. J. 14495.3 µmol TE/100 g. total antioxidant capacity intake (ORAC) from the diet was 8537. (Swedish Mammography Cohort. Based on the food consumption data in the NHANES (2001-02) hydrophilic ORAC intake was estimated to be 4650 units per day [6]. A significant trend for decreased risk of endometrial cancer was observed in the population group that was © 2013 by NWPII. dietary hydrophilic ORAC intake was <5266. Using controlled diets providing 10 servings of fruits and vegetables ORAC intake increased to 8600 units of ORAC per day and was increased to 10800 units with the addition of 2 servings of broccoli. However. 5266-8663.000 units per day are possible from foods if selected properly. 57]. In women with a cardiovascular disease history. Thus. The estimated intake of lipophilic ORAC from this same data was estimated to be 166 units per day [6]. but these intakes were only obtained in the top quintile of subjects in the Swedish study. 1007 controls). doi: 10. 12. some broad recommendations can be made based upon recent epidemiological studies and studies of absorption of antioxidant phytochemicals and their effects on in vivo antioxidant status and their ability to prevent postprandial oxidative stress. 134 . n = 32. In the Mayo Clinic Case-Control study [49] (603 cases. In this subgroup.5099/aj130200126 estimate is similar to that calculated from the USDA food intake data of 2385 units per person per day [6]. This Am. >12519 units/day for the lowest to the highest quartiles.444 units ORAC per day) were more likely to have a history of hemorrhagic stroke [58]. the relative risk for total stroke and cerebral infarction was least in those consuming more than 12.021 units/day. 2080 units/day of hydrophilic antioxidants would be ingested when 350 g of vegetables a day are consumed [55]. Hence. Sci. However. is not possible for total dietary antioxidants (measured by ORAC or any other antioxidant capacity assay). Biomed. ORAC intakes as high as 18.561 subjects) [56. as has been done for vitamins A. and E. Data from food intake records of 30 subjects in a controlled nutrition study indicated that hydrophilic ORAC intake was 7405 units/day/person [1 unit = 1 micromole of Trolox Equivalents (TE)].

gastric cancer. doi: 10.000 participants) dietary ORAC intake was 5600 ORAC units per day [8.232 mg gallic acid equivalents of total phenolics [50]. Prior and coworkers [3] developed a relationship between dietary energy intake and ORAC intake that indicated that 4. These data have provided the first definitive data on ORAC intake and the levels that might be needed for improved health outcomes.282 units of ORAC per day or more than 2. including polyphenols on human Am. Increased fruit and vegetable consumption has also been associated with reduced risk of mortality in men from one study [41]. ORAC intake was 8500 in the lowest quintile and 18. we begin to have better estimates of the quantities of antioxidants we may need in our diet. 135 . The need for increased vegetable consumption has been known and recommended for many years. the USDA ORAC food database has been removed from their website. cigarette smoke. In the Singapore Health Study (63. disease situations. All rights reserved. consumption of a mixture of high antioxidant foods would be prudent to provide for this variability. Because of the difference in the ability of different phytochemicals to quench free radicals. J. Furthermore. pesticides. 57]. and pulmonary function.000 ORAC units per day. endometrial cancer. consumption of sources of antioxidants is important with each meal. The following statement was provided as a reason for its removal: “USDA’s Nutrient Data Laboratory (NDL) removed the USDA ORAC Database for Selected Foods from the NDL website due to mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds. ORAC intakes of at least 12. From 3 different studies in the United States. In studies reviewed in this report. increased dietary intake of total antioxidant capacity has been associated with reduced risk for ischemic stroke. consumption with antioxidant rich foods can reverse the oxidative stress resulting from consumption of an antioxidant free meal. 5(2). dietary ORAC intake ranged from 4600 to 7400 units of ORAC per day. Furthermore. Unfortunately. 2013. from the recent studies. it seems clear that their reasoning for removal of the data base was not based upon the recent scientific literature. Other sources of free radicals such as dietary prooxidants. drugs. hypertension. © 2013 by NWPII. etc would increase the need for antioxidants.200 ORAC units per day and from risk of endometrial cancer with consumption of more than 16. The basis for proposing a relationship with energy intake was that free radicals are produced in the process of energy metabolism due to inefficiencies in the process. smog.000 or more should be recommended for reduced risk for the diseases studied and intakes of less than ~7000 units of ORAC per day is likely responsible for increased risk for some diseases.5099/aj130200126 health” [59]. 126-139. In Sweden. A greater risk for hemorrhagic stroke was observed with consumption of less than 7. Sci.000 in the highest quintile [56. recently with the availability of the USDA ORAC food database and other total antioxidant databases. From the available data.400 ORAC units per day [58]. From the available postprandial data on plasma antioxidant capacity.6 µmoles TE of antioxidant capacity should be consumed for every Kcal consumed. Protection from stroke was observed in individuals consuming greater than 12. Biomed. it has been difficult to differentiate between increased intake of fruits and vegetables and antioxidant intake because an increase in fruit and vegetable consumption is also associated with increased antioxidant intake and also with increased plasma antioxidant capacity. Conclusions In early studies of dietary antioxidant intake. 9]. These recommendations are in line with consumption of 7 to 10 servings of fruits and vegetables with some of those foods containing the higher amounts of ORAC. However. data has become available on antioxidant intake and relationship with some disease outcomes.consuming more that 16. Before any of the data from the large epidemiological studies was available on dietary ORAC intake was available. From published data presented in this review. This estimate was considered a minimum as it only accounted for oxidative stress associated with energy metabolism.

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