|
|
|
|
2 Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 and 3 Department of Foods and Nutrition, Kookmin University, Seoul, Korea 136-702
* To whom correspondence should be addressed. E-mail: song{at}msu.edu.
| ABSTRACT |
|---|
|
|
|---|
19-y-old adults (n = 8335), and did not include pregnant and/or lactating women. Flavonoid intake of U.S. adults was estimated by the USDA flavonoid databases matched with a 24-h dietary recall in NHANES 1999–2002. The serum CRP concentration was higher in women, older adults, blacks, and smokers, and in those with high BMI or low exercise level, and in those taking NSAID, than in their counterparts (P < 0.01). Intakes of apples and vegetables were inversely associated with serum CRP concentrations after adjusting for covariates (P < 0.05). Total flavonoid and also individual flavonol, anthocyanidin, and isoflavone intakes were inversely associated with serum CRP concentration after adjusting for the covariates (P < 0.05). Among the flavonoid compounds investigated, quercetin, kaempferol, malvidin, peonidin, daidzein, and genistein had inverse associations with serum CRP concentration (P < 0.05). These associations did not change even after the additional adjustment for fruit and vegetable consumption. Our findings demonstrate that intake of dietary flavonoids is inversely associated with serum CRP concentrations in U.S. adults. Intake of flavonoid-rich foods may thus reduce inflammation-mediated chronic diseases.
| Introduction |
|---|
|
|
|---|
Even though several population-based observational or randomized clinical trial studies (9–13) have reported that serum CRP concentrations are inversely associated with dietary intake of fruits, vegetables, and tea, which are rich in polyphenolic antioxidants such as flavonoids (14,15), data directly delineating the protective mechanisms are scant. One proposed mechanism for the benefit of dietary flavonoids is the antioxidant properties (16–23). These polyphenols are effective scavengers of reactive oxygen species (24) and can inhibit lipid peroxidation through chelation of transition metal ions (25,26) or their chain breaking antioxidants (27). These properties suggest that flavonoids might prevent LDL oxidation, an early key inflammatory event in the development of atherosclerosis (28). However, studies on the antiinflammatory effects of specific flavonoid compounds or flavonoid-rich foods are still controversial (29–31). We speculate that, in addition to being confounded by high baseline antioxidant vitamin intakes and sociodemographic status of the participants, inaccurate estimates of dietary intake of flavonoids due to incomplete flavonoid food composition data in those studies have contributed to the inconsistent findings (11,30,32,33).
Recently, we reported estimates of total dietary flavonoid intake of U.S. population based on the recently released USDA flavonoid databases matched with food consumption data from the NHANES 1999–2002 (14). Building upon our previous research scheme to estimate flavonoid intake, we aimed to test the associations between dietary flavonoid intake and serum CRP concentrations among U.S. adults after adjusting for dietary, sociodemographic, and lifestyle factors, which are known to be associated with serum CRP concentration.
| Subjects and Methods |
|---|
|
|
|---|
2 mo of age in the 50 states and the District of Columbia. All interviewed persons were invited to the mobile examination center, where the 24-h dietary recall (DR) was administered.
A total of 8335 individuals
19 y of age who completed the 24-h DR and had serum CRP concentration data in the NHANES 1999–2002 were included in this study. To minimize physiological variations, we excluded pregnant and nursing women's data.
The U.S. adult population was grouped by sociodemographic and lifestyle variables: age (19–30, 31–50, 51–70, 70+ y), gender, ethnicity (non-Hispanic white; non-Hispanic black; Mexican-American; others), BMI (<20, 20–24.9, 25–29.9,
30), poverty income ratios (<1.85,
1.85), alcohol consumption (yes or no to "at least 12 drinks per year"), current smoking (yes or no to "current smoking" and "smoked cigarettes, cigars, or pipes and/or used chewing tobacco or snuff at least once during the past 30 d"), exercise levels [expressed on the metabolic equivalent (MET) score calculated by combining the intensity level of the leisure time activities reported, average duration, and frequency], and nonsteroidal antiinflammatory drug (NSAID) use (yes or no to "any prescribed NSAID use in past month").
Food consumption data. Dietary flavonoid intake was estimated based on one 24-h DR (midnight to midnight) of the NHANES 1999–2002 (34,35). DR data contained all foods and beverages consumed by the respondents except for plain drinking water. To minimize errors from misreporting, we excluded individuals with unreliable or incomplete DR records as noted by the National Center for Health Statistics (36).
Serum CRP concentrations. Specimen collection and processing were carried out by the NHANES Laboratory/Medical Technologists Procedures Manual (37). Serum CRP was measured using a Behring Nephelometer. The limit of detection was 0.2 mg/L.
USDA flavonoid databases. Details of the datasets used in this study were reported in our previous study (14). Briefly, we created 1 flavonoid database from 2 different data sets released in recent years: 1) the USDA database for the Flavonoid Content of Selected Food (38) includes the most abundant 19 individual flavonoid compounds in 5 flavonoid subgroups (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanidins) in 234 selected foods; and 2) the USDA-Iowa State University Database on the Isoflavone Content of Foods (39) was created by extensive sampling of 108 soy-containing foods and subsequent analysis at Iowa State University. The combined 1 flavonoid database consisted of 24 flavonoid compounds: flavonols (quercetin, kaempferol, myricetin, isorhamnetin), flavones (luteolin, apigenin), flavanones (eriodictyol, hesperetin, naringenin), flavan-3-ols (catechins, epicatechins, theaflavins, thearubigins), anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin), and isoflavones (daidzein, genistein, glycitein, biochanin A, formononetin).
To improve the accuracy of the estimated flavonoid intake, we expanded the flavonoid database according to the preestablished protocol that has been described extensively in a separate publication (14).
Estimation of flavonoid intakes. We matched the NHANES food consumption data with the flavonoid database following the steps described in our previous work: 1) conversion of food items in NHANES DR to USDA Standard Reference codes using food recipe book and food description data file for NHANES food codes; 2) weight adjustment using moisture content; 3) code modification using the USDA food unit conversion search program; and 4) linking food intake data with the flavonoid database. Daily individual flavonoid intake from selected foods was determined by multiplying the content of the individual flavonoid (mg aglycone equivalent/100 g food) by the daily consumption (g/d) of the selected food item. Estimated total intake of individual flavonoids was the sum of individual flavonoid intakes from all food sources reported in the 24-h DR. Total flavonoid intake was determined by the summation of total intake of individual flavonoids.
Statistical analyses. All statistical analyses were carried out with SAS software, release 8.1, 2000 (SAS Institute) and the Survey Data Analysis for multi-stage sample designs professional software package (SUDAAN, release 8.0.2, 2003, Research Triangle Institute). SUDAAN was used to increase the accuracy and validity of the results through computing variance estimates and test statistics for a stratified, multistage probability survey design. Sample weights were applied to all analyses to account for the unequal probability of selection, noncoverage, and nonresponse bias resulting from oversampling of low-income persons, adolescents, the elderly, African-Americans, and Mexican-Americans.
ANOVA techniques were used to test the association between serum CRP concentrations and sociodemographic and lifestyle factors. To test the linear trends in serum CRP concentrations by the intakes of antioxidant vitamins, subjects were divided into quartiles according to their vitamin C, E, and carotene intakes, respectively. Covariates that were found to be independent predictors of serum CRP concentration and adjusted for the analysis included gender, age, ethnicity, BMI, smoking, exercise, NSAID use, alcohol consumption, and total energy intake.
Serum CRP concentration was reported as geometric means to normalize the right-skewed data distribution. A cutoff point of >3 mg/L was used to define elevated CRP concentration in this study, because it has been shown to be an independent predictor of future cardiovascular risk (40,41).
To test the linear trends in serum CRP concentrations by the consumption of flavonoid-rich foods, all subjects who did not consume the food item or group in a 24-h DR were classified as nonconsumers and the remaining consumers were divided into tertiles by the amount of consumption. Apples, citrus fruits and juices, fruitaids and drinks, "mixture mainly grains," tea, vegetables, and wines were selected as the top flavonoid-rich foods (14). Mixture mainly grains included mixtures having a grain product as a main ingredient, such as burritos, tacos, pizza, egg rolls, quiche, spaghetti with sauce, rice and pasta mixtures; frozen meals in which the main course is a grain mixture; and noodle and rice soups. Tea intake was estimated by adding the consumption of all tea: leaf, herbal, nonspecified, brewed, ready-to drink, instant, powdered, and sweetened.
Analysis for linear trends was conducted to test the associations between the total/individual flavonoid intake and serum CRP concentrations after adjusting for covariates that were independently related to serum CRP concentration in our sample: gender; age; ethnicity; BMI; smoking; exercise; NSAID use; alcohol consumption; total energy; vitamin C, vitamin E, carotene intakes; and other flavonoid intakes. We tested if the flavonoid intake is a predictor of serum CRP concentration independent from fruit and vegetable consumption. To identify the major flavonoid compounds that exert the antiinflammatory effect, the 13 most-consumed flavonoid compounds were tested for linear trends in relation to serum CRP concentration.
| Results |
|---|
|
|
|---|
|
|
3 mg/L (P < 0.05) (Table 3). Controlling for antioxidant vitamin intake did not affect the results (data are not shown).
|
|
|
| Discussion |
|---|
|
|
|---|
Flavonoids were shown to inhibit the synthesis and gene expression of cytokines (3). Nuclear factor (NF)-
B, an oxidant-sensitive upstream regulator of proinflammatory mediator synthesis, plays a key role in this process (43). Oxidative stress leads to NF-
B activation and DNA binding (44,45). As a result, the inflammatory cascade is triggered and CRP is subsequently produced (46). Antioxidants were shown to block NF-
B activation and DNA binding (45,47).
In this cross-sectional study, we also noted that the consumption of apples and vegetables was associated with low serum CRP concentrations in accordance with previously reported experimental studies (10,48). We assert that the antioxidants in apples and vegetables, i.e. carotenoids, vitamin E, vitamin C, and flavonoids, may contribute to this antiinflammatory effect. In our recent reports, we documented that flavonoids were major dietary antioxidant sources in the American diet, with only 14% of dietary antioxidants was contributed by vitamin C alone (15). Fruit and fruit juices were the major dietary sources of flavonols, flavanones, and anthocyanidins; vegetables and vegetable products of flavonols and flavan-3-ols (14).
The extent of antioxidant effect exerted by a food is determined by the amount of all antioxidants in the food and the antioxidant capacity of the individual antioxidant compounds in the food. In our previous study, citrus fruit and citrus fruit juices, primarily including oranges, exhibited the highest antioxidant amount of 147 mg vitamin C equivalent/100 g fresh food and contributed 33% of total antioxidants obtained from daily fruit consumption. Apple was reported as the next highest contributor to the U.S. diet accounting for 25% of the total antioxidant from fruit consumption. Apple has been reported by others as an important source of antioxidants in the U.S. diet (49–51). In this study, the apple consumption was inversely associated with serum CRP concentration; however, the intake of citrus fruits and citrus fruit juices was not. This inconsistent result may be attributed to the differences in the antioxidant capacities and compositions between citrus fruits and apples. Citrus fruits and fruit juices that are rich in hesperetin and naringenin have lower antioxidant capacities compared with quercitin and catechins that are high in apples (52).
Tea is a major food source of flavonoids, but the protective role of tea in reducing inflammation process has not yet been fully documented (9,13,53,54). In a recent epidemiological study conducted with 1031 healthy Belgian men, De Bacquer et al. (9) reported that serum CRP concentrations were inversely associated with tea consumption. In another double-blind, placebo-controlled trial with 37 healthy nonsmoking men, regular tea consumption reduced platelet activation and plasma CRP concentrations (13). By contrast, in a randomized trial with 64 smokers with no previous medical history of chronic diseases, drinking black or green tea did not affect levels of inflammation or endothelial cardiovascular risk factors (53). Most previous studies have limitations in their study design with small sample size and lack of control for other antioxidant intakes or inflammation-related lifestyle factors including smoking, alcohol consumption, and BMI and physical activity levels.
In this study, only 21% of the adults reported consuming tea and tea consumption was not associated with serum CRP concentration. In addition, the major tea flavonoids (catechins and epicatechins) had no remarkable antiinflammatory effect in this study. The NHANES 1999–2002 dataset did not have detailed information on the types of tea. Our study focused on the association between flavonoid intake and serum CRP concentration. Further studies are needed to determine the effect of specific food consumption and integrated flavonoid intakes from all food sources eaten during certain periods for any possible changes in inflammatory response levels.
In contrast to the recently reported Women's Health Study (WHS) (29), our findings showed that total flavonoid intakes were inversely associated with serum CRP concentrations. A possible reason for this difference may be due to the fact that WHS estimated total flavonoid intake by summating only the 5 major flavonols and flavones (quercetin, kaempferol, luteolin, myricetin, and apigenin). This has been the major limitation of the previous studies on the estimation of flavonoid intake (55,56). WHS used the food composition database that was originally generated in the Netherlands and later supplemented with values for American foods (57). Therefore, in associating the total flavonoid intake with serum CRP concentrations, the investigators were unable to include the intake from flavan-3-ols, major tea catechins, in estimating the total flavonoids intake of the subjects. Anthocyanidins from fruits and wines are another important group of flavonoids to be considered in the estimation. We cannot overemphasize that the success of scientific research depends on the accuracy and reliability of the food composition data used.
In this study, we observed an inverse association between isoflavone intake and serum CRP concentrations. This result contrasts with the findings of other isoflavone supplementation trials in which CRP was measured (31,58,59). However, in a recently reported randomized, double-blind, placebo-controlled, dietary crossover intervention trial of 117 European postmenopausal women, intake of soy-isoflavone-enriched foods lowered CRP concentrations (60).
Our findings are interpreted based on several assumptions. First, the USDA food composition databases were constructed based on U.S. representative food samples including varying cultivars, geographic origin, growing seasons, agricultural practices, and analytical methods. Second, this study focused on flavonoid intake, not bioavailability and metabolism in the human body or changes during processing and food preparation. Third, this study includes major flavonoids of 6 flavonoid subgroups consisting of 24 individual flavonoid compounds. Fourth, despite within-person variability, a 24-h DR can produce adequate estimates of mean intake of a group that can be useful for contrasting the dietary status of the group with different levels of risk factors for certain diseases (61).
In summary, our study demonstrated that daily intake of specific foods and flavonoids have antiinflammatory potential beyond the benefits of fruit and vegetable consumption and thus may reduce CVD risks. This opens the door to further research into the implicated relationship between flavonoid intake and other CVD risks. This study focused on flavonoid intake based on food composition tables and further research is needed to study individual bioavailability, metabolism in the human body, and changes during processing and food preparation.
| FOOTNOTES |
|---|
4 Present address: Department of Nutrition and Dietetics, East Carolina University, Greenville, NC 27858. ![]()
5 Abbreviations used: CRP, C-reactive protein; CVD, cardiovascular disease; DR, dietary recall; MET, metabolic equivalent; NF, nuclear factor; NSAID, nonsteroidal antiinflammatory drug; WHS, Women's Health Study. ![]()
Manuscript received 27 July 2007. Initial review completed 29 August 2007. Revision accepted 18 January 2008.
| LITERATURE CITED |
|---|
|
|
|---|
1. Breslow JL. Cardiovascular disease burden increases, NIH funding decreases. Nat Med. 1997;3:600–1.[CrossRef][Medline]
2. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–26.
3. Middleton E Jr, Kandaswami C, Theoharides T. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 2000;52:673–751.
4. Lowe G. The relationship between infection, inflammation, and cardiovascular disease: an overview. Ann Periodontol. 2001;6:1–8.[Medline]
5. Patrick L, Uzick M. Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev. 2001;6:248–71.[Medline]
6. Calabró P, Willerson J, Yeh E. Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation. 2003;108:1930–2.
7. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–43.
8. Verma S, Devaraj S, Jialal I. C-Reactive protein promotes atherothrombosis. Circulation. 2006;113:2135–50.[Medline]
9. De Bacquer D, Clays E, Delanghe J, De Backer G. Epidemiological evidence for an association between habitual tea consumption and markers of chronic inflammation. Atherosclerosis. 2006;189:428–35.[Medline]
10. Gao X, Bermudez O, Tucker K. Plasma C-reactive protein and homocysteine concentrations are related to frequent fruit and vegetable intake in Hispanic and non-Hispanic white elders. J Nutr. 2004;134:913–8.
11. Widlansky M, Duffy S, Hamburg N, Gokce N, Warden B, Wiseman S, Keaney JJ, Frei B, Vita J. Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med. 2005;38:499–506.[CrossRef][Medline]
12. Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu F, Willett W. Fruit and vegetable intakes, C-reactive protein, and the metabolic syndrome. Am J Clin Nutr. 2006;84:1489–97.
13. Steptoe A, Gibson E, Vuononvirta R, Hamer M, Wardle J, Rycroft J, Martin J, Erusalimsky J. The effects of chronic tea intake on platelet activation and inflammation: a double-blind placebo controlled trial. Atherosclerosis. 2007;193:277–82.[Medline]
14. Chun O, Chung S, Song W. Estimated dietary flavonoid intakes and major food sources of U.S. adults. J Nutr. 2007;137:1244–52.
15. Chun OK, Kim D-O, Smith NL, Schroeder D, Han JT, Lee CY. Daily consumption of phenolics and total antioxidant capacity from fruit and vegetables in the American diet. J Sci Food Agric. 2005;85:1715–24.
16. Barnes S, Boersma B, Patel R, Kirk M, Darley-Usmar VM, Kim H, Xu J. Isoflavonoids and chronic disease: mechanisms of action. Biofactors. 2000;12:209–15.[Medline]
17. Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A, Hakulinen T, Aromaa A. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr. 2002;76:560–8.
18. Liu RH. Protective role of phytochemicals in whole foods: implications for chronic disease prevention. Appl Biotechnol Food Sci Policy. 2003;1:39–46.
19. Pietrzik K. Antioxidant vitamins, cancer and cardiovascular disease. N Engl J Med. 1996;335:1065–9.
20. Frei B. Cardiovascular disease and nutrient antioxidants: role of low-density lipoprotein oxidation. Crit Rev Food Sci Nutr. 1995;35:83–98.[Medline]
21. Kris-Etherton PM, Hecker KD, Bonanome A, Coval SM, Binkoski AE, Hilpert KF, Griel AE, Etherton TD. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med. 2002;113:S71–88.[CrossRef][Medline]
22. National Research Council, Committee on Diet and Health. Diet and health: implications for reducing chronic disease risk. Washington, DC: National Academy Press; 1989.
23. WHO. Diet, nutrition and the prevention of chronic diseases. Geneva: WHO; 2003.
24. Robak J, Gryglewski R. Flavonoids are scavengers of superoxide anions. Biochem Pharmacol. 1988;37:837–41.[CrossRef][Medline]
25. Srichairatanakool S, Ounjaijean S, Thephinlap C, Khansuwan U, Phisalpong C, Fucharoen S. Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload. Hemoglobin. 2006;30:311–27.[Medline]
26. Leopoldini M, Russo N, Chiodo S, Toscano M. Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem. 2006;54:6343–51.[CrossRef][Medline]
27. van Acker F, Schouten O, Haenen G, van der Vijgh W, Bast A. Flavonoids can replace alpha-tocopherol as an antioxidant. FEBS Lett. 2000;473:145–8.[CrossRef][Medline]
28. Lind L. Circulating markers of inflammation and atherosclerosis. Atherosclerosis. 2003;169:203–14.[CrossRef][Medline]
29. Song Y, Manson J, Buring J, Sesso H, Liu S. Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. J Am Coll Nutr. 2005;24:376–84.
30. Mathur S, Devaraj S, Grundy S, Jialal I. Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans. J Nutr. 2002;132:3663–7.
31. Jenkins D, Kendall C, Connelly P, Jackson C, Parker T, Faulkner D, Vidgen E. Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism. 2002;51:919–24.[CrossRef][Medline]
32. Maron D. Flavonoids for reduction of atherosclerotic risk. Curr Atheroscler Rep. 2004;6:73–8.[Medline]
33. Brighenti F, Valtuena S, Pellegrini N, Ardigo D, Del Rio D, Salvatore S, Piatti P, Serafini M, Zavaroni I. Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects. Br J Nutr. 2005;93:619–25.[CrossRef][Medline]
34. National Center for Health Statistics. National Health and Nutrition Examination Survey, 1999–2000 Data Files. Hyattsvilles (MD): CDC; 2002.
35. National Center for Health Statistics. National Health and Nutrition Examination Survey, 2001–2002 Data Files. Hyattsville (MD): CDC; 2004.
36. Botman S, Moore T, Moriarity C, Parsons V. Design and estimation for the national health interview survey, 1995–2004. Vital Health Stat 2. 2000;130:1–31.
37. National Center for Health Statistics. General information about the NHANES 1999–2000, laboratory methodology and public data files. Hyattsville, MD: CDC; 2002.
38. Agricultural Research Service. Database for the Flavonoid Content of Selected Foods. Beltsville (MD): USDA; 2003.
39. Agricultural Research Service. USDA-Iowa State University Database on the Isoflavone Content of Foods, Release 1.3: Beltsville (MD): USDA; 2002.
40. Blake G, Rifai N, Buring J, Ridker P. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108:2993–9.
41. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363–9.
42. Ridker P, Morrow D. C-reactive protein, inflammation, and coronary risk. Cardiol Clin. 2003;21:315–25.[CrossRef][Medline]
43. Meydani S, Wu D, Santos M, Hayek M. Antioxidants and immune response in aged persons: overview of present evidence. Am J Clin Nutr. 1995;62:S1462–76.
44. Lee J, Burckart G. Nuclear factor kappa B: important transcription factor and therapeutic target. J Clin Pharmacol. 1998;38:981–93.
45. Palozza P, Serini S, Torsello A, Di Nicuolo F, Piccioni E, Ubaldi V, Pioli C, Wolf F, Calviello G. β-Carotene regulates NF-B DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells. J Nutr. 2003;133:381–8.
46. Wanner C, Metzger T. C-reactive protein a marker for all-cause and cardiovascular mortality in haemodialysis patients. Nephrol Dial Transplant. 2002;17 Suppl 8:29–32.
47. Omoya T, Shimizu I, Zhou Y, Okamura Y, Inoue H, Lu G, Itonaga M, Honda H, Nomura M, et al. Effects of idoxifene and estradiol on NF-
B activation in cultured rat hepatocytes undergoing oxidative stress. Liver. 2001;21:183–91.[CrossRef][Medline]
48. Boekholdt S, Meuwese M, Day N, Luben R, Welch A, Wareham N, Khaw K. Plasma concentrations of ascorbic acid and C-reactive protein, and risk of future coronary artery disease, in apparently healthy men and women: the EPIC-Norfolk prospective population study. Br J Nutr. 2006;96:516–22.[Medline]
49. Eberhardt MV, Lee CY, Liu RH. Antioxidant activity of fresh apples. Nature. 2000;405:903–4.[Medline]
50. Lee CY, Smith NL. Apples: an important source of antioxidants in the American diet. N Y Fruit Quarterly. 2000;8:15–7.
51. Lu Y, Foo LY. Antioxidant and radical scavenging activities of polyphenols from apple pomace. Food Chem. 2000;68:81–5.
52. Kim D-O, Lee C. Comprehensive study on vitamin C equivalent antioxidant capacity (VCEAC) of various polyphenolics in scavenging a free radical and its structural relationship. Crit Rev Food Sci Nutr. 2004;44:253–73.[Medline]
53. de Maat M, Pijl H, Kluft C, Princen H. Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals. Eur J Clin Nutr. 2000;54:757–63.[CrossRef][Medline]
54. Fukino Y, Shimbo M, Aoki N, Okubo T, Iso H. Randomized controlled trial for an effect of green tea consumption on insulin resistance and inflammation markers. J Nutr Sci Vitaminol (Tokyo). 2005;51:335–42.[Medline]
55. Hertog MGL, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995;155:381–6.
56. Hertog MGL, Hollman PCH, Katan MB, Kromhout D. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands. Nutr Cancer. 1993;20:21–9.[Medline]
57. Rimm E, Giovannucci E, Stampfer M, Colditz G, Litin L, Willett W. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol. 1992;135:1114–26.
58. Nikander E, Metsa-Heikkila M, Tiitinen A, Ylikorkala O. Evidence of a lack of effect of a phytoestrogen regimen on the levels of C-reactive protein, E-selectin, and nitrate in postmenopausal women. J Clin Endocrinol Metab. 2003;88:5180–5.
59. McVeigh B, Dillingham B, Lampe J, Duncan A. Effect of soy protein varying in isoflavone content on serum lipids in healthy young men. Am J Clin Nutr. 2006;83:244–51.
60. Hall W, Vafeiadou K, Hallund J, Bugel S, Koebnick C, Reimann M, Ferrari M, Branca F, Talbot D, et al. Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr. 2005;82:1260–8.
61. Byers T. Nutrition monitoring and surveillance. In: Willett W, editor. Nutritional epidemiology. 2nd ed. New York: Oxford University Press; 1992. p. 347–56.
This article has been cited by other articles:
![]() |
M. J. Puglisi and M. L. Fernandez Modulation of C-Reactive Protein, Tumor Necrosis Factor-{alpha}, and Adiponectin by Diet, Exercise, and Weight Loss J. Nutr., December 1, 2008; 138(12): 2293 - 2296. [Abstract] [Full Text] [PDF] |
||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||