The potential role of phytochemicals in wholegrain cereals for the prevention of type-2 diabetes

Nutrition Journal

Anthony R Bird¹  Damien P Belobrajdic¹ 

[1] CSIRO Animal Food & Health Sciences, Adelaide, SA, 5000, Australia

关键词: Inflammation;    Oxidative stress;    Type-2 diabetes;    Phytochemical;    Wholegrain;   

Others  :  806788
DOI  :  10.1186/1475-2891-12-62

 received in 2013-02-27, accepted in 2013-04-24,  发布年份 2013

【 摘 要 】

Diets high in wholegrains are associated with a 20-30% reduction in risk of developing type-2 diabetes (T2D), which is attributed to a variety of wholegrain components, notably dietary fibre, vitamins, minerals and phytochemicals. Most phytochemicals function as antioxidants in vitro and have the potential to mitigate oxidative stress and inflammation which are implicated in the pathogenesis of T2D. In this review we compare the content and bioavailability of phytochemicals in wheat, barley, rice, rye and oat varieties and critically evaluate the evidence for wholegrain cereals and cereal fractions increasing plasma phytochemical concentrations and reducing oxidative stress and inflammation in humans. Phytochemical content varies considerably within and among the major cereal varieties. Differences in genetics and agro-climatic conditions explain much of the variation. For a number of the major phytochemicals, such as phenolics and flavanoids, their content in grains may be high but because these compounds are tightly bound to the cell wall matrix, their bioavailability is often limited. Clinical trials show that postprandial plasma phenolic concentrations are increased after consumption of wholegrain wheat or wheat bran however the magnitude of the response is usually modest and transient. Whether this is sufficient to bolster antioxidant defences and translates into improved health outcomes is still uncertain. Increased phytochemical bioavailability may be achieved through bio-processing of grains but the improvements so far are small and have not yet led to changes in clinical or physiological markers associated with reduced risk of T2D. Furthermore, the effect of wholegrain cereals and cereal fractions on biomarkers of oxidative stress or strengthening antioxidant defence in healthy individuals is generally small or nonexistent, whereas biomarkers of systemic inflammation tend to be reduced in people consuming high intakes of wholegrains. Future dietary intervention studies seeking to establish a direct role of phytochemicals in mediating the metabolic health benefits of wholegrains, and their potential for mitigating disease progression, should consider using varieties that deliver the highest possible levels of bioavailable phytochemicals in the context of whole foods and diets. Both postprandial and prolonged responses in systemic phytochemical concentrations and markers of inflammation and oxidative stress should be assessed along with changes related to health outcomes in healthy individuals as well as those with metabolic disease.

【 授权许可】

   
2013 Belobrajdic and Bird; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Shaw JE, Sicree RA, Zimmet PZ: Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010, 87:4-14.
• [2]Whiting DR, Guariguata L, Weil C, Shaw J: IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011, 94:311-321.
• [3]Walgate R: Diabetes research for developing countries. N Biotechnol 2008, 25:111-116.
• [4]Misra A, Singhal N, Khurana L: Obesity, the metabolic syndrome, and type 2 diabetes in developing countries: role of dietary fats and oils. J Am Coll Nutr 2010, 29:289S-301S.
• [5]Fitzgerald MA, Rahman S, Resurreccion AP, Concepcion J, Daygon VD, Dipti SS, Kabir KA, Klingner B, Morell M, Bird A: Identification of a major genetic determinant of glycaemic index in rice. Rice 2011, 4:66-74.
• [6]Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393-403.
• [7]Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, Colditz GA, Willett WC: Whole-grain intake and the risk of type 2 diabetes: a prospective study in men. Am J Clin Nutr 2002, 76:535-540.
• [8]Hodge AM, English DR, O'Dea K, Giles GG: Dietary patterns and diabetes incidence in the Melbourne Collaborative Cohort Study. Am J Epidemiol 2007, 165:603-610.
• [9]Brunner EJ, Mosdol A, Witte DR, Martikainen P, Stafford M, Shipley MJ, Marmot MG: Dietary patterns and 15-y risks of major coronary events, diabetes, and mortality. Am J Clin Nutr 2008, 87:1414-1421.
• [10]Nettleton JA, McKeown NM, Kanoni S, Lemaitre RN, Hivert MF, Ngwa J, van Rooij FJ, Sonestedt E, Wojczynski MK, Ye Z, et al.: Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies. Diabetes Care 2010, 33:2684-2691.
• [11]Meyer KA, Kushi LH, Jacobs DR Jr, Slavin J, Sellers TA, Folsom AR: Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 2000, 71:921-930.
• [12]McKeown NM, Meigs JB, Liu S, Wilson PW, Jacques PF: Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. Am J Clin Nutr 2002, 76:390-398.
• [13]Pereira MA, Jacobs DR Jr, Pins JJ, Raatz SK, Gross MD, Slavin JL, Seaquist ER: Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. Am J Clin Nutr 2002, 75:848-855.
• [14]van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB: Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002, 136:201-209.
• [15]Murtaugh MA, Jacobs DR Jr, Jacob B, Steffen LM, Marquart L: Epidemiological support for the protection of whole grains against diabetes. Proc Nutr Soc 2003, 62:143-149.
• [16]Venn BJ, Mann JI: Cereal grains, legumes and diabetes. Eur J Clin Nutr 2004, 58:1443-1461.
• [17]de Munter JS, Hu FB, Spiegelman D, Franz M, van Dam RM: Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. PLoS Med 2007, 4:e261.
• [18]Priebe MG, van Binsbergen JJ, de Vos R, Vonk RJ: Whole grain foods for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev 2008, 23(1):CD006061.
• [19]Jang Y, Lee JH, Kim OY, Park HY, Lee SY: Consumption of whole grain and legume powder reduces insulin demand, lipid peroxidation, and plasma homocysteine concentrations in patients with coronary artery disease: randomized controlled clinical trial. Arterioscler Thromb Vasc Biol 2001, 21:2065-2071.
• [20]Lutsey PL, Jacobs DR Jr, Kori S, Mayer-Davis E, Shea S, Steffen LM, Szklo M, Tracy R: Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: The MESA Study. Br J Nutr 2007, 98:397-405.
• [21]Rave K, Roggen K, Dellweg S, Heise T, Tom Dieck H: Improvement of insulin resistance after diet with a whole-grain based dietary product: results of a randomized, controlled cross-over study in obese subjects with elevated fasting blood glucose. Br J Nutr 2007, 98:929-936.
• [22]Hallfrisch J, Fac N, Behall KM: Mechanisms of the effects of grains on insulin and glucose responses. J Am Coll Nutr 2000, 19:320S-325S.
• [23]Slavin J: Why whole grains are protective: biological mechanisms. Proc Nutr Soc 2003, 62:129-134.
• [24]Smith CE, Tucker KL: Health benefits of cereal fibre: a review of clinical trials. Nutr Res Rev 2011, 15:1-14.
• [25]Jonnalagadda SS, Harnack L, Liu RH, McKeown N, Seal C, Liu S, Fahey GC: Putting the whole grain puzzle together: health benefits associated with whole grains–summary of American Society for Nutrition 2010 Satellite Symposium. J Nutr 2011, 141:1011S-1022S.
• [26]Harris KA, Kris-Etherton PM: Effects of whole grains on coronary heart disease risk. Curr Atheroscler Rep 2010, 12:368-376.
• [27]Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H: Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med 2007, 167:956-965.
• [28]Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC: Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 2001, 345:790-797.
• [29]Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I: Dietary glycemic index: health implications. J Am Coll Nutr 2009, 28(Suppl):446S-449S.
• [30]Sluijs I, Beulens JW, der AD V, Spijkerman AM, Grobbee DE, Van der Schouw YT: Dietary intake of total, animal, and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Diabetes Care 2010, 33:43-48.
• [31]Barclay AW, Petocz P, McMillan-Price J, Flood VM, Prvan T, Mitchell P, Brand-Miller JC: Glycemic index, glycemic load, and chronic disease risk–a meta-analysis of observational studies. Am J Clin Nutr 2008, 87:627-637.
• [32]Halton TL, Liu S, Manson JE, Hu FB: Low-carbohydrate-diet score and risk of type 2 diabetes in women. Am J Clin Nutr 2008, 87:339-346.
• [33]Livesey G, Taylor R, Hulshof T, Howlett J: Glycemic response and health–a systematic review and meta-analysis: relations between dietary glycemic properties and health outcomes. Am J Clin Nutr 2008, 87:258S-268S.
• [34]Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I: Carbohydrates–the good, the bad and the whole grain. Asia Pac J Clin Nutr 2008, 17(Suppl 1):16-19.
• [35]Okarter N, Liu RH: Health benefits of whole grain phytochemicals. Crit Rev Food Sci Nutr 2010, 50:193-208.
• [36]Ceriello A, Motz E: Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004, 24:816-823.
• [37]Dandona P, Aljada A, Chaudhuri A, Mohanty P: Endothelial dysfunction, inflammation and diabetes. Rev Endocr Metab Disord 2004, 5:189-197.
• [38]Robertson RP: Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 2004, 279:42351-42354.
• [39]Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414:813-820.
• [40]Niedowicz DM, Daleke DL: The role of oxidative stress in diabetic complications. Cell Biochem Biophys 2005, 43:289-330.
• [41]Cardona F, Tunez I, Tasset I, Montilla P, Collantes E, Tinahones FJ: Fat overload aggravates oxidative stress in patients with the metabolic syndrome. Eur J Clin Invest 2008, 38:510-515.
• [42]Pizent A, Pavlovic M, Jurasovic J, Dodig S, Pasalic D, Mujagic R: Antioxidants, trace elements and metabolic syndrome in elderly subjects. J Nutr Health Aging 2010, 14:866-871.
• [43]Levitan EB, Cook NR, Stampfer MJ, Ridker PM, Rexrode KM, Buring JE, Manson JE, Liu S: Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein. Metabolism 2008, 57:437-443.
• [44]Guo W, Kong E, Meydani M: Dietary polyphenols, inflammation, and cancer. Nutr Cancer 2009, 61:807-810.
• [45]Anson NM, Aura AM, Selinheimo E, Mattila I, Poutanen K, van den Berg R, Havenaar R, Bast A, Haenen GR: Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo. J Nutr 2011, 141:137-143.
• [46]Hanhineva K, Torronen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkanen H, Poutanen K: Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci 2010, 11:1365-1402.
• [47]Salas-Salvado J, Martinez-Gonzalez MA, Bullo M, Ros E: The role of diet in the prevention of type 2 diabetes. Nutr Metab Cardiovasc Dis 2011, 21(Suppl 2):B32-48.
• [48]Fardet A: New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 2010, 23:65-134.
• [49]Adom KK, Sorrells ME, Liu RH: Phytochemicals and antioxidant activity of milled fractions of different wheat varieties. J Agric Food Chem 2005, 53:2297-2306.
• [50]Slavin JL, Jacobs D, Marquart L: Grain processing and nutrition. Crit Rev Biotechnol 2001, 21:49-66.
• [51]Bryngelsson S, Dimberg LH, Kamal-Eldin A: Effects of commercial processing on levels of antioxidants in oats (Avena sativa L.). J Agric Food Chem 2002, 50:1890-1896.
• [52]Qiu Y, Liu Q, Beta T: Antioxidant activity of commercial wild rice and identification of flavonoid compounds in active fractions. J Agric Food Chem 2009, 57:7543-7551.
• [53]Xu SY, Cheng HJ, Guo YY, Ding SR: Amino acid contents of barley grains in relation to cultivars and cultivation conditions. Zhejiang Agricultural Science 1988, 254-259.
• [54]Fickler J, Fontaine J, Heimbeck W: The amino acid composition of feedstuffs. Ridgefield Park, NJ; 2001.
• [55]Lee TT, Wang MM, Hou RC, Chen LJ, Su RC, Wang CS, Tzen JT: Enhanced methionine and cysteine levels in transgenic rice seeds by the accumulation of sesame 2S albumin. Biosci Biotechnol Biochem 2003, 67:1699-1705.
• [56]Council NAoS-NR: Joint United States-Canadian tables of Feed Composition. 2nd edition. Washington, D.C; 1964.
• [57]Gibson C, Lyons G, Choi B, Park S, Stewart D: Selenium enriched barley. Biofortification to improve human health. Hobart, Australia: 12th Australian Barley Technical Symposium; 2005.
• [58]Williams PN, Lombi E, Sun GX, Scheckel K, Zhu YG, Feng X, Zhu J, Carey AM, Adomako E, Lawgali Y, et al.: Selenium characterization in the global rice supply chain. Environ Sci Technol 2009, 43:6024-6030.
• [59]Eurola M, Hietaniemi V, Kontturi M, Tuuri H, Kangas A, Niskanen M, Saastamoinen M: Selium content of Finnish oats in 1997–1999: effect of cultivars and cultivation techniques. Ag Food Sci 2004, 13:46-53.
• [60]Fardet A, Llorach R, Orsoni A, Martin JF, Pujos-Guillot E, Lapierre C, Scalbert A: Metabolomics provide new insight on the metabolism of dietary phytochemicals in rats. J Nutr 2008, 138:1282-1287.
• [61]Ward JL, Poutanen K, Gebruers K, Piironen V, Lampi AM, Nystrom L, Andersson AA, Aman P, Boros D, Rakszegi M, et al.: The HEALTHGRAIN Cereal Diversity Screen: concept, results, and prospects. J Agric Food Chem 2008, 56:9699-9709.
• [62]Bruce SJ, Guy PA, Rezzi S, Ross AB: Quantitative measurement of betaine and free choline in plasma, cereals and cereal products by isotope dilution LC-MS/MS. J Agric Food Chem 2010, 58:2055-2061.
• [63]Britz SJ, Prasad PV, Moreau RA, Allen LH Jr, Kremer DF, Boote KJ: Influence of growth temperature on the amounts of tocopherols, tocotrienols, and gamma-oryzanol in brown rice. J Agric Food Chem 2007, 55:7559-7565.
• [64]Nystrom L, Lampi A-M, Andersson AAM, Kamal-Eldin A, Gebruers K, Courtin CM, Delcour JA, Li L, Ward JL, Fras A, et al.: Phytochemicals and Dietary Fiber Components in Rye Varieties in the HEALTHGRAIN Diversity Screen. J Agric Food Chem 2008, 56:9758-9766.
• [65]Barnes PJ: Cereal tocopherols. Amsterdam: Elsevier; 1983.
• [66]Lasztity R, Berndorfer-Kraszner E, Huszar M: On the presence and distribution of some bioactive agents in oat varieties. New York: Academic Press; 1980.
• [67]Ehrenbergerova J, Belcrediova N, Pryma J, Vaculova K, Newman CW: Effect of cultivar, year grown, and cropping system on the content of tocopherols and tocotrienols in grains of hulled and hulless barley. Plant Foods Hum Nutr 2006, 61:145-150.
• [68]Shewry PR, Piironen V, Lampi A-M, Nystrom L, Li L, Rakszegi M, Fras A, Boros D, Gebruers K, Courtin CM, et al.: Phytochemical and Fiber Components in Oat Varieties in the HEALTHGRAIN Diversity Screen. J Agric Food Chem 2008, 56:9777-9784.
• [69]Zilic S, Sukalovic VH, Dodig D, Maksimovic V, Maksimovic M, Basic Z: Antioxidant activity of small grain cereals caused by phenolics and lipid soluble antioxidants. J Cereal Sci 2011, 54:417-424.
• [70]Evans LE, Dedio W, Hill RD: Variability in the alkylresorcinol content of rye grains. Can J Plant Sci 1973, 53:485-488.
• [71]Dimberg LH, Molteberg EL, Solheim R, Frølich W: Variation in Oat Groats Due to Variety, Storage and Heat Treatment. I: Phenolic Compounds. J Cereal Sci 1996, 24:263-272.
• [72]Emmons CL DMP: Antioxidant activity and phenolic content of oat as affected by cultivar and location. Crop Sci 2001, 41:1676-1681.
• [73]de Zwart FJ, Slow S, Payne RJ, Lever M, George PM, Gerrard JA, Chambers ST: Glycine betaine and glycine betaine analogues in common foods. Food Chem 2003, 83:197-204.
• [74]Andersson AAM, Lampi A-M, Nystrom L, Piironen V, Li L, Ward JL, Gebruers K, Courtin CM, Delcour JA, Boros D, et al.: Phytochemical and Dietary Fiber Components in Barley Varieties in the HEALTHGRAIN Diversity Screen. J Agric Food Chem 2008, 56:9767-9776.
• [75]Baublis AJ, Lu C, Clydesdale FM, Decker EA: Potential of wheat-based breakfast cereals as a source of dietary antioxidants. J Am Coll Nutr 2000, 19:308S-311S.
• [76]Mattila P, Pihlava JM, Hellstrom J: Contents of phenolic acids, alkyl- and alkenylresorcinols, and avenanthramides in commercial grain products. J Agric Food Chem 2005, 53:8290-8295.
• [77]Parikka K, Rowland IR, Welch RW, Wahala K: In vitro antioxidant activity and antigenotoxicity of 5-n-alkylresorcinols. J Agric Food Chem 2006, 54:1646-1650.
• [78]Adom KK, Sorrells ME, Liu RH: Phytochemical profiles and antioxidant activity of wheat varieties. J Agric Food Chem 2003, 51:7825-7834.
• [79]Lampi A-M, Nurmi T, Ollilainen V, Piironen V: Tocopherols and Tocotrienols in Wheat Genotypes in the HEALTHGRAIN Diversity Screen. J Agric Food Chem 2008, 56:9716-9721.
• [80]Davis KR, Peters LJ, LeTourneau D: Variability of the vitamin content of wheat. Cereal Foods World 1984, 29:364-370.
• [81]Clarke B, Liang R, Morell MK, Bird AR, Jenkins CL, Li Z: Gene expression in a starch synthase IIa mutant of barley: changes in the level of gene transcription and grain composition. Funct Integr Genomics 2008, 8:211-221.
• [82]Bird AR, Vuaran MS, King RA, Noakes M, Keogh J, Morell MK, Topping DL: Wholegrain foods made from a novel high-amylose barley variety (Himalaya 292) improve indices of bowel health in human subjects. Br J Nutr 2008, 99:1032-1040.
• [83]King RA, Noakes M, Bird AR, Morell MK, Topping DL: An extruded cereal made from a high amylose barley cultivar has a low glycemic index and lower plasma insulin response than one made from a standard barley. J Cereal Sci 2008, 48:526-530.
• [84]Ross AB, Aman P, Andersson R, Kamal-Eldin A: Chromatographic analysis of alkylresorcinols and their metabolites. J Chromatogr A 2004, 1054:157-164.
• [85]Peterson DM, Qureshi AA: Genotype and environment effects on tocols of barley and oats. Cereal Chem 1993, 70:157-162.
• [86]Peterson DM: Oat Antioxidants. J Cereal Sci 2001, 33:115-129.
• [87]Bergman CJ, Xu Z: Genotype and environment effects on tocopherol, tocotrienol, and ç-oryzanol contents of southern U.S. rice. Cereal Chem 2003, 80:446-449.
• [88]Miller A, Engel KH: Content of gamma-oryzanol and composition of steryl ferulates in brown rice (Oryza sativa L.) of European origin. J Agric Food Chem 2006, 54:8127-8133.
• [89]Moore J, Hao Z, Zhou K, Luther M, Costa J, Yu LL: Carotenoid, tocopherol, phenolic acid, and antioxidant properties of Maryland-grown soft wheat. J Agric Food Chem 2005, 53:6649-6657.
• [90]Lampi AM, Nurmi T, Piironen V: Effects of the environment and genotype on tocopherols and tocotrienols in wheat in the HEALTHGRAIN diversity screen. J Agric Food Chem 2010, 58:9306-9313.
• [91]Fernandez-Orozco R, Li L, Harflett C, Shewry PR, Ward JL: Effects of Environment and Genotype on Phenolic Acids in Wheat in the HEALTHGRAIN Diversity Screen. J Agric Food Chem 2010, 58:9341-9352.
• [92]Li L, Shewry PR, Ward JL: Phenolic Acids in Wheat Varieties in the HEALTHGRAIN Diversity Screen. J Agric Food Chem 2008, 56:9732-9739.
• [93]Heaney RP: Factors influencing the measurement of bioavailability, taking calcium as a model. J Nutr 2001, 131:1344S-1348S.
• [94]Riedl J, Linseisen J, Hoffmann J, Wolfram G: Some Dietary Fibers Reduce the Absorption of Carotenoids in Women. J Nutr 1999, 129:2170-2176.
• [95]Fenech M, Noakes M, Clifton P, Topping D: Aleurone Flour Is a Rich Source of Bioavailable Folate in Humans. J Nutr 1999, 129:1114-1119.
• [96]Scholz S, Williamson G: Interactions affecting the Bioavailability of dietary polyphenols in vivo. Int J Vitam Nutr Res 2007, 77:224-235.
• [97]Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L: Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004, 79:727-747.
• [98]Price R, Welch R, Lee-Manion A, Bradbury I, Strain JJ: Total phenolics and antioxidant potential in plasma and urine of humans after consumption of wheat bran. Cereal Chem 2008, 85:152-157.
• [99]Ross AB, Kamal-Eldin A, Lundin EA, Zhang JX, Hallmans G, Aman P: Cereal alkylresorcinols are absorbed by humans. J Nutr 2003, 133:2222-2224.
• [100]Linko-Parvinen AM, Landberg R, Tikkanen MJ, Adlercreutz H, Penalvo JL: Alkylresorcinols from whole-grain wheat and rye are transported in human plasma lipoproteins. J Nutr 2007, 137:1137-1142.
• [101]Landberg R, Linko AM, Kamal-Eldin A, Vessby B, Adlercreutz H, Aman P: Human plasma kinetics and relative bioavailability of alkylresorcinols after intake of rye bran. J Nutr 2006, 136:2760-2765.
• [102]Kamal-Eldin A, Poruru A, Eliasson AC, Aman P: Alkylresorcinols as antioxidants: hydrogen donation and peroxyl radical-scavenging effects. J Sci Food Agric 2001, 81:353-356.
• [103]Harder H, Tetens I, Let MB, Meyer AS: Rye bran bread intake elevates urinary excretion of ferulic acid in humans, but does not affect the susceptibility of LDL to oxidation ex vivo. Eur J Nutr 2004, 43:230-236.
• [104]Craig SA: Betaine in human nutrition. Am J Clin Nutr 2004, 80:539-549.
• [105]Price RK, Keaveney EM, Hamill LL, Wallace JM, Ward M, Ueland PM, McNulty H, Strain JJ, Parker MJ, Welch RW: Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults. J Nutr 2010, 140:2153-2157.
• [106]Likes R, Madl RL, Zeisel SH, Craig SA: The betaine and choline content of a whole wheat flour compared to other mill streams. J Cereal Sci 2007, 46:93-95.
• [107]Hallberg L, Hulthen L: Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 2000, 71:1147-1160.
• [108]Serafini M, Laranjinha JA, Almeida LM, Maiani G: Inhibition of human LDL lipid peroxidation by phenol-rich beverages and their impact on plasma total antioxidant capacity in humans. J Nutr Biochem 2000, 11:585-590.
• [109]van der Burg-Koorevaar MC, Miret S, Duchateau GS: Effect of milk and brewing method on black tea catechin bioaccessibility. J Agric Food Chem 2011, 59:7752-7758.
• [110]Reddy VC, Vidya Sagar GV, Sreeramulu D, Venu L, Raghunath M: Addition of milk does not alter the antioxidant activity of black tea. Ann Nutr Metab 2005, 49:189-195.
• [111]van het Hof KH, Kivits GA, Weststrate JA, Tijburg LB: Bioavailability of catechins from tea: the effect of milk. Eur J Clin Nutr 1998, 52:356-359.
• [112]Anson NM, Selinheimo E, Havenaar R, Aura AM, Mattila I, Lehtinen P, Bast A, Poutanen K, Haenen GR: Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds. J Agric Food Chem 2009, 57:6148-6155.
• [113]Kern SM, Bennett RN, Mellon FA, Kroon PA, Garcia-Conesa MT: Absorption of hydroxycinnamates in humans after high-bran cereal consumption. J Agric Food Chem 2003, 51:6050-6055.
• [114]Rice-Evans C: Flavonoid antioxidants. Curr Med Chem 2001, 8:797-807.
• [115]Scalbert A, Morand C, Manach C, Remesy C: Absorption and metabolism of polyphenols in the gut and impact on health. Biomed Pharmacother 2002, 56:276-282.
• [116]Selma MV, Espin JC, Tomas-Barberan FA: Interaction between Phenolics and Gut Microbiota: Role in Human Health. J Agric Food Chem 2009, 57:6485-6501.
• [117]Hervert-Hernandez D, Goni I: Dietary Polyphenols and Human Gut Microbiota: a Review. Food Reviews International 2011, 27:154-169.
• [118]Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa MT: Intestinal release and uptake of phenolic antioxidant diferulic acids. Free Radic Biol Med 2001, 31:304-314.
• [119]Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa MT: Esterase activity able to hydrolyze dietary antioxidant hydroxycinnamates is distributed along the intestine of mammals. J Agric Food Chem 2001, 49:5679-5684.
• [120]Kroon PA, Faulds CB, Ryden P, Robertson JA, Williamson G: Release of covalently bound ferulic acid from fiber in the human colon. J Agric Food Chem 1997, 45:661-667.
• [121]Rondini L, Peyrat-Maillard M-N, Marsset-Baglieri A, Fromentin G, Durand P, Tomé D, Prost M, Berset C: Bound Ferulic Acid from Bran Is More Bioavailable than the Free Compound in Rat. J Agric Food Chem 2004, 52:4338-4343.
• [122]Kim SH, Lee SS, Kim JY, Kim JH, Lee Da H: Meal replacement with mixed rice is more effective than white rice in weight control, while improving antioxidant enzyme activity in obese women. Nutrition research (New York, NY) 2008, 28:66-71.
• [123]Enright L, Slavin J: No effect of 14 day consumption of whole grain diet compared to refined grain diet on antioxidant measures in healthy, young subjects: a pilot study. Nutr J 2010, 9:12.
• [124]Andersson A, Tengblad S, Karlstrom B, Kamal-Eldin A, Landberg R, Basu S, Aman P, Vessby B: Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects. J Nutr 2007, 137:1401-1407.
• [125]Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007, 39:44-84.
• [126]Chen CY, Milbury PE, Collins FW, Blumberg JB: Avenanthramides are bioavailable and have antioxidant activity in humans after acute consumption of an enriched mixture from oats. J Nutr 2007, 137:1375-1382.
• [127]Bruce B, Spiller GA, Klevay LM, Gallagher SK: A diet high in whole and unrefined foods favorably alters lipids, antioxidant defenses, and colon function. J Am Coll Nutr 2000, 19:61-67.
• [128]Myhrstad MC, Carlsen H, Nordstrom O, Blomhoff R, Moskaug JO: Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med 2002, 32:386-393.
• [129]Moskaug JO, Carlsen H, Myhrstad MC, Blomhoff R: Polyphenols and glutathione synthesis regulation. Am J Clin Nutr 2005, 81:277S-283S.
• [130]Thomson CD, Ong LK, Robinson MF: Effects of supplementation with high-selenium wheat bread on selenium, glutathione peroxidase and related enzymes in blood components of New Zealand residents. Am J Clin Nutr 1985, 41:1015-1022.
• [131]Barclay MNI, Macpherson A: Selenium content of wheat for bread making in Scotland and the relationship between glutathione-peroxidase levels in whole-blood and bread consumption. Br J Nutr 1992, 68:261-270.
• [132]Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, Hurst R: Selenium in human health and disease. Antioxid Redox Signal 2011, 14:1337-1383.
• [133]del Molino IMM, Rojo B, Martínez-Carrasco R, Pérez P: Varietal differences in amino acid composition of wheat (Triticum aestivum L) grain. J Sci Food Agric 48:177-188.
• [134]Wang Q, Han P, Zhang M, Xia M, Zhu H, Ma J, Hou M, Tang Z, Ling W: Supplementation of black rice pigment fraction improves antioxidant and anti-inflammatory status in patients with coronary heart disease. Asia Pac J Clin Nutr 2007, 16(Suppl 1):295-301.
• [135]Seidel C, Boehm V, Vogelsang H, Wagner A, Persin C, Glei M, Pool-Zobel BL, Jahreis G: Influence of prebiotics and antioxidants in bread on the immune system, antioxidative status and antioxidative capacity in male smokers and non-smokers. Br J Nutr 2007, 97:349-356.
• [136]Lotito SB, Frei B: Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: Cause, consequence, or epiphenomenon? Free Radic Biol Med 2006, 41:1727-1746.
• [137]Erel O: A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004, 37:277-285.
• [138]Bartlett HE, Eperjesi F: Nutritional supplementation for type 2 diabetes: a systematic review. Ophthalmic Physiol Opt 2008, 28:503-523.
• [139]Golbidi S, Ebadi SA, Laher I: Antioxidants in the treatment of diabetes. Curr Diabetes Rev 2011, 7:106-125.
• [140]Beattie R, Lee A, Strain J: Evaluation of the in vivo antioxidant activity of wheat bran in human subjects. Proc Nutr Soc 2003, 62:17A.
• [141]Ou B, Huang D, Hampsch-Woodill M, Flanagan JA, Deemer EK: Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. J Agric Food Chem 2002, 50:3122-3128.
• [142]Niki E: Assessment of antioxidant capacity in vitro and in vivo. Free Radic Biol Med 2010, 49:503-515.
• [143]Chuang SC, Vermeulen R, Sharabiani MT, Sacerdote C, Fatemeh SH, Berrino F, Krogh V, Palli D, Panico S, Tumino R, et al.: The intake of grain fibers modulates cytokine levels in blood. Biomarkers 2011, 16:504-510.
• [144]de Mello VD, Schwab U, Kolehmainen M, Koenig W, Siloaho M, Poutanen K, Mykkanen H, Uusitupa M: A diet high in fatty fish, bilberries and wholegrain products improves markers of endothelial function and inflammation in individuals with impaired glucose metabolism in a randomised controlled trial: the Sysdimet study. Diabetologia 2011, 54:2755-2767.
• [145]Oliveira A, Rodriguez-Artalejo F, Lopes C: The association of fruits, vegetables, antioxidant vitamins and fibre intake with high-sensitivity C-reactive protein: sex and body mass index interactions. Eur J Clin Nutr 2009, 63:1345-1352.
• [146]Herder C, Peltonen M, Koenig W, Sutfels K, Lindstrom J, Martin S, Ilanne-Parikka P, Eriksson JG, Aunola S, Keinanen-Kiukaanniemi S, et al.: Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study. Diabetologia 2009, 52:433-442.
• [147]Al-Lahham SH, Peppelenbosch MP, Roelofsen H, Vonk RJ, Venema K: Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim Biophys Acta 1801, 2010:1175-1183.
• [148]Roelofsen H, Priebe MG, Vonk RJ: The interaction of short-chain fatty acids with adipose tissue: relevance for prevention of type 2 diabetes. Benef Microbes 2010, 1:433-437.
• [149]Verbeke K, Ferchaud-Roucher V, Preston T, Small AC, Henckaerts L, Krempf M, Wang H, Vonk RJ, Priebe MG: Influence of the type of indigestible carbohydrate on plasma and urine short-chain fatty acid profiles in healthy human volunteers. Eur J Clin Nutr 2010, 64:678-684.
• [150]Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG: Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology 1995, 108:218-224.
• [151]Lichtman SN, Keku J, Schwab JH, Sartor RB: Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology 1991, 100:513-519.
• [152]Lichtman SN, Sartor RB, Keku J, Schwab JH: Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology 1990, 98:414-423.
• [153]Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, et al.: Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009, 58:1091-1103.