{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T03:37:23Z","timestamp":1770521843048,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US Department of Agriculture, Agricultural Research Service","award":["cooperative agreement 58-1950-014"],"award-info":[{"award-number":["cooperative agreement 58-1950-014"]}]},{"name":"The Kellogg Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>While dietary fiber plays an important role in the health benefits associated with whole grain consumption, other ingredients concentrated in the outer bran layer, including alkylresorcinols, lignans, phenolic acids, phytosterols, and tocols, may also contribute to these outcomes. To determine the acute bioavailability and pharmacokinetics of the major phytochemicals found in barley and oats, we conducted a randomized, three-way crossover trial in 13 healthy subjects, aged 40\u201370 years with a body mass index (BMI) of 27\u201335.9 kg\/m2. After a two-day run-in period following a diet low in phytochemicals, subjects were randomized to receive muffins made with either 48 g whole oat flour, whole barley flour, or refined wheat flour plus cellulose (control), with a one-week washout period between each intervention. At the same time, an oral glucose tolerance test was administered. In addition to plasma phytochemical concentrations, glucose and insulin responses, biomarkers of antioxidant activity, lipid peroxidation, inflammation, and vascular remodeling were determined over a 24-h period. There was no significant effect on acute bioavailability or pharmacokinetics of major phytochemicals. Administered concurrently with a glucose bolus, the source of whole grains did not attenuate the post-prandial response of markers of glucoregulation and insulin sensitivity, inflammation, nor vascular remodeling compared to the refined grain control. No significant differences were observed in the bioavailability or postprandial effects between whole-oat and whole-barley compared to a refined wheat control when administered with a glucose challenge. These null results may be due, in part, to the inclusion criteria for the subjects, dose of the whole grains, and concurrent acute administration of the whole grains with the glucose bolus.<\/jats:p>","DOI":"10.3390\/nu8120813","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T10:53:16Z","timestamp":1481799196000},"page":"813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Phytochemical Pharmacokinetics and Bioactivity of Oat and Barley Flour: A Randomized Crossover Trial"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8353-3106","authenticated-orcid":false,"given":"Caleigh","family":"Sawicki","sequence":"first","affiliation":[{"name":"Nutritional Epidemiology, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston 02111, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"McKay","sequence":"additional","affiliation":[{"name":"Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston 02111, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"McKeown","sequence":"additional","affiliation":[{"name":"Nutritional Epidemiology, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston 02111, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Dallal","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston 02111, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston 02111, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-8635","authenticated-orcid":false,"given":"Jeffrey","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston 02111, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.3945\/jn.113.179473","article-title":"Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain","volume":"142","author":"Ye","year":"2012","journal-title":"J. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s10654-013-9852-5","article-title":"Whole grain and refined grain consumption and the risk of type 2 diabetes: A systematic review and dose\u2013response meta-analysis of cohort studies","volume":"28","author":"Aune","year":"2013","journal-title":"Eur. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3945\/ajcn.115.109165","article-title":"Whole-grain and blood lipid changes in apparently healthy adults: A systematic review and meta-analysis of randomized controlled studies","volume":"102","author":"Ross","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.numecd.2006.12.008","article-title":"Whole grain intake and cardiovascular disease: A meta-analysis","volume":"18","author":"Mellen","year":"2008","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Huang, T., Xu, M., Lee, A., Cho, S., and Qi, L. (2015). Consumption of whole grains and cereal fiber and total and cause-specific mortality: Prospective analysis of 367,442 individuals. BMC Med., 13.","DOI":"10.1186\/s12916-015-0294-7"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1001\/jamainternmed.2014.6283","article-title":"Association between dietary whole grain intake and risk of mortality: Two large prospective studies in US men and women","volume":"175","author":"Wu","year":"2015","journal-title":"JAMA Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s11883-004-0081-y","article-title":"Whole grain intake and cardiovascular disease: A review","volume":"6","author":"Jacobs","year":"2004","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"326S","DOI":"10.1080\/07315724.2000.10718968","article-title":"Fiber from whole grains, but not refined grains, is inversely associated with all-cause mortality in older women: The Iowa women\u2019s health study","volume":"19","author":"Jacobs","year":"2000","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3945\/jn.110.127720","article-title":"Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo","volume":"141","author":"Aura","year":"2011","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1021\/jf011222z","article-title":"Effects of commercial processing on levels of antioxidants in oats (Avena sativa L.)","volume":"50","author":"Bryngelsson","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/10408390802248734","article-title":"Health benefits of whole grain phytochemicals","volume":"50","author":"Okarter","year":"2010","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ejcn.2013.25","article-title":"Review of human studies investigating the post-prandial blood-glucose lowering ability of oat and barley food products","volume":"67","author":"Tosh","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1753-4887.2011.00401.x","article-title":"Cholesterol-lowering effects of oat \u03b2-glucan","volume":"69","author":"Othman","year":"2011","journal-title":"Nutr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3945\/ajcn.114.088120","article-title":"Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: Role of polyphenols bound to cereal dietary fiber","volume":"101","author":"Vitaglione","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.3390\/nu5051471","article-title":"Major cereal grain fibers and psyllium in relation to cardiovascular health","volume":"5","author":"Bernstein","year":"2013","journal-title":"Nutrients"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/jn\/137.6.1375","article-title":"Avenanthramides Are bioavailable and have antioxidant activity in humans after acute consumption of an enriched mixture from oats","volume":"137","author":"Chen","year":"2007","journal-title":"J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/chrsci\/49.3.221","article-title":"Simultaneous measurement of three tocopherols, all-trans-retinol, and eight carotenoids in human plasma by isocratic liquid chromatography","volume":"49","author":"Liu","year":"2011","journal-title":"J. Chromatogr. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1007\/s00394-015-0936-8","article-title":"Comparison of plasma alkylresorcinols (AR) and urinary AR metabolites as biomarkers of compliance in a short-term, whole-grain intervention study","volume":"55","author":"McKeown","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1093\/jn\/135.6.1366","article-title":"Flavonoids from almond skins are bioavailable and act synergistically with vitamins C and E to enhance hamster and human LDL resistance to oxidation","volume":"135","author":"Chen","year":"2005","journal-title":"J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The ferric reducing ability of plasma (FRAP) as a measure of \u201cantioxidant power\u201d: The FRAP assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0076-6879(94)33044-1","article-title":"Measurement of protein thiol groups and glutathione in plasma","volume":"Volume 233","author":"Hu","year":"1994","journal-title":"Methods in Enzymology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/jn\/136.2.404","article-title":"Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: A randomized, double-blind, crossover trial","volume":"136","author":"Nielsen","year":"2006","journal-title":"J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1017\/S0954422410000041","article-title":"New hypotheses for the health-protective mechanisms of whole-grain cereals: What is beyond fibre?","volume":"23","author":"Fardet","year":"2010","journal-title":"Nutr. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Belobrajdic, D.P., and Bird, A.R. (2013). The potential role of phytochemicals in wholegrain cereals for the prevention of type-2 diabetes. Nutr. J., 12.","DOI":"10.1186\/1475-2891-12-62"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.17221\/401\/2014-CJFS","article-title":"Ferulic acid in cereals\u2014A review","volume":"33","author":"Boz","year":"2015","journal-title":"Czech J. Food Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.nut.2012.02.010","article-title":"Digestive and physiologic effects of a wheat bran extract, arabino-xylan-oligosaccharide, in breakfast cereal","volume":"28","author":"Maki","year":"2012","journal-title":"Nutrition"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1094\/CCHEM-85-2-0152","article-title":"Total phenolics and antioxidant potential in plasma and urine of humans after consumption of wheat bran","volume":"85","author":"Price","year":"2008","journal-title":"Cereal Chem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/ajcn\/80.5.1185","article-title":"Diets containing barley significantly reduce lipids in mildly hypercholesterolemic men and women","volume":"80","author":"Behall","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/j.jada.2006.06.010","article-title":"Whole-grain diets reduce blood pressure in mildly hypercholesterolemic men and women","volume":"106","author":"Behall","year":"2006","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.numecd.2009.03.025","article-title":"Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people","volume":"20","author":"Giacco","year":"2010","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1093\/jn\/137.6.1401","article-title":"Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects","volume":"137","author":"Andersson","year":"2007","journal-title":"J. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1017\/S0007114510000644","article-title":"Markers of cardiovascular risk are not changed by increased whole-grain intake: The WHOLEheart study, a randomised, controlled dietary intervention","volume":"104","author":"Brownlee","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Enright, L., and Slavin, J. (2010). 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., 9.","DOI":"10.1186\/1475-2891-9-12"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s00394-004-0463-5","article-title":"Rye bran bread intake elevates urinary excretion of ferulic acid in humans, but does not affect the susceptibility of LDL to oxidation ex vivo","volume":"43","author":"Harder","year":"2004","journal-title":"Eur. J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1017\/S0007114507328626","article-title":"Influence of prebiotics and antioxidants in bread on the immune system, antioxidative status and antioxidative capacity in male smokers and non-smokers","volume":"97","author":"Seidel","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1002\/mnfr.201300582","article-title":"Whole-grain intake favorably affects markers of systemic inflammation in obese children: A randomized controlled crossover clinical trial","volume":"58","author":"Hajihashemi","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.clnu.2013.01.016","article-title":"Effects of rye and whole wheat versus refined cereal foods on metabolic risk factors: A randomised controlled two-centre intervention study","volume":"32","author":"Giacco","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.3945\/jn.112.164996","article-title":"Fecal lactic acid bacteria increased in adolescents randomized to whole-grain but not refined-grain foods, whereas inflammatory cytokine production decreased equally with both interventions","volume":"142","author":"Nieves","year":"2012","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/ajcn\/53.6.1425","article-title":"Oat gum lowers glucose and insulin after an oral glucose load","volume":"53","author":"Braaten","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2337\/diacare.19.8.831","article-title":"Effects of breakfast cereals containing various amounts of beta-glucan fibers on plasma glucose and insulin responses in NIDDM subjects","volume":"19","author":"Tappy","year":"1996","journal-title":"Diabetes Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.nutres.2009.07.003","article-title":"High-molecular-weight barley beta-glucan in chapatis (unleavened Indian flatbread) lowers glycemic index","volume":"29","author":"Thondre","year":"2009","journal-title":"Nutr. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/NT.0000000000000082","article-title":"Evidence-based approach to fiber supplements and clinically meaningful health benefits, part 1: What to look for and how to recommend an effective fiber therapy","volume":"50","author":"McRorie","year":"2015","journal-title":"Nutr. Today"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s00394-009-0778-3","article-title":"Glucose and insulin responses to whole grain breakfasts varying in soluble fiber, beta-glucan: A dose response study in obese women with increased risk for insulin resistance","volume":"48","author":"Kim","year":"2009","journal-title":"Eur. J. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/ajcn\/78.2.221","article-title":"Cholesterol-lowering effect of beta-glucan from oat bran in mildly hypercholesterolemic subjects may decrease when beta-glucan is incorporated into bread and cookies","volume":"78","author":"Kerckhoffs","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7543","DOI":"10.1021\/jf901074b","article-title":"Antioxidant activity of commercial wild rice and identification of flavonoid compounds in active fractions","volume":"57","author":"Qiu","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.cell.2015.11.001","article-title":"Personalized Nutrition by Prediction of Glycemic Responses","volume":"163","author":"Zeevi","year":"2015","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.copbio.2012.09.009","article-title":"Gut metabotypes govern health effects of dietary polyphenols","volume":"24","author":"Bolca","year":"2013","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Matthan, N.R., Ausman, L.M., Meng, H., Tighiouart, H., and Lichtenstein, A.H. (2016). Estimating the reliability of glycemic index values and potential sources of methodological and biological variability. Am. J. Clin. Nutr., 104.","DOI":"10.3945\/ajcn.116.137208"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/8\/12\/813\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:37Z","timestamp":1760210917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/8\/12\/813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":48,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["nu8120813"],"URL":"https:\/\/doi.org\/10.3390\/nu8120813","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]}}}