{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:15:51Z","timestamp":1762506951771,"version":"3.41.0"},"reference-count":58,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,8,16]]},"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cardiovascular diseases (CVD) are the leading cause of mortality worldwide and diet is an important contributor to CVD risk. Thus, several food derivatives are being investigated for their beneficial impact on reducing cardiometabolic risk factors, either in risk groups or in healthy population as a preventive measure. Wheat germ is a food by-product with high nutritional value, especially as a concentrated source of dietary fibre and essential fatty acids, but its incorporation into the diet has been rare up to now. Previous studies do not clarify the hypothesised potential causal relationship between the consumption of wheat germ and benefits for human health.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>We are conducting a randomised, double-blinded, crossover, placebo-controlled clinical trial designed to assess the physiological effects of daily consumption of wheat germ-enriched bread (containing 6\u2005g of wheat germ) compared with non-enriched bread, over a 4-week period with a 15-week follow-up, in a healthy human population. A total of 55 participants (healthy volunteers, aged 18\u201360) have been recruited from the Porto metropolitan area in northern Portugal. Our aim is to evaluate the health effects of wheat germ on blood cholesterol and triglycerides, postprandial glycaemic response, gastrointestinal function and discomfort, and changes in intestinal microbiota and insulin resistance as secondary outcomes. The study follows the best practices for evaluating health claims in food according to the European Food Safety Authority (EFSA) scientific opinion, namely random allocation, double blinding, reporting methods to measure and maximise compliance, and validated outcomes with beneficial physiological effects as recommended by EFSA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>The study has been approved by the Health Ethics Committee of S\u00e3o Jo\u00e3o Hospital Centre (156-15) and the Ethics Committee of Faculty of Medicine of the University of Porto (PCEDCSS-FMUP07\/2015). Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02405507\" ext-link-type=\"uri\">NCT02405507<\/jats:ext-link>; pre-results.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2016-013098","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T10:55:43Z","timestamp":1479120943000},"page":"e013098","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Can wheat germ have a beneficial effect on human health? A study protocol for a randomised crossover controlled trial to evaluate its health effects"],"prefix":"10.1136","volume":"6","clinical-trial-number":[{"clinical-trial-number":"nct02405507","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Andr\u00e9","family":"Moreira-Ros\u00e1rio","sequence":"first","affiliation":[]},{"given":"Helder","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"Concei\u00e7\u00e3o","family":"Calhau","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds Filipe","family":"Azevedo","sequence":"additional","affiliation":[]}],"member":"239","published-online":{"date-parts":[[2016,11,10]]},"reference":[{"key":"2024051611114596000_6.11.e013098.1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/oxfordjournals.aje.a113788","article-title":"Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to nutrient intake","volume":"119","author":"McGee","year":"1984","journal-title":"Am J Epidemiol"},{"key":"2024051611114596000_6.11.e013098.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.03.013"},{"key":"2024051611114596000_6.11.e013098.3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004487"},{"key":"2024051611114596000_6.11.e013098.4","doi-asserted-by":"crossref","first-page":"274S","DOI":"10.1093\/ajcn\/76.1.274S","article-title":"Glycemic index, glycemic load, and risk of type 2 diabetes","volume":"76","author":"Willett","year":"2002","journal-title":"Am J Clin Nutr"},{"key":"2024051611114596000_6.11.e013098.5","doi-asserted-by":"publisher","DOI":"10.1159\/000338102"},{"key":"2024051611114596000_6.11.e013098.6","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2015-008222"},{"key":"2024051611114596000_6.11.e013098.7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1046\/j.1365-277X.2003.00498.x","article-title":"The opinion of Dutch dietitians about functional foods","volume":"17","author":"de Jong","year":"2004","journal-title":"J Hum Nutr Diet"},{"key":"2024051611114596000_6.11.e013098.8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1475-2891-13-44","article-title":"Functional food awareness and perceptions in relation to information sources in older adults","volume":"13","author":"Vella","year":"2014","journal-title":"Nutr J"},{"key":"2024051611114596000_6.11.e013098.9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.021101"},{"key":"2024051611114596000_6.11.e013098.10","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i2716"},{"key":"2024051611114596000_6.11.e013098.11","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.086108"},{"key":"2024051611114596000_6.11.e013098.12","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to beta glucans and maintenance of normal blood cholesterol concentrations (ID 754, 755, 757, 801, 1465, 2934) and maintenance or achievement of a normal body weight (ID 820, 823) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA Journal 2009; 7(9):1254. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/1254 (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2009.1254"},{"key":"2024051611114596000_6.11.e013098.13","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to walnuts and maintenance of normal blood LDL-cholesterol concentrations (ID 1156, 1158) and improvement of endothelium-dependent vasodilation (ID 1155, 1157) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA Journal 2011;9(4):2074. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/2074 (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2011.2074"},{"key":"2024051611114596000_6.11.e013098.14","doi-asserted-by":"publisher","DOI":"10.3109\/09637486.2011.633898"},{"key":"2024051611114596000_6.11.e013098.15","doi-asserted-by":"crossref","first-page":"6215","DOI":"10.1021\/jf000478m","article-title":"Some nutritional and functional properties of defatted wheat germ protein","volume":"48","author":"Ge","year":"2000","journal-title":"J Agric Food Chem"},{"key":"2024051611114596000_6.11.e013098.16","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.ultsonch.2013.04.005","article-title":"Pretreatment of defatted wheat germ proteins (by-products of flour mill industry) using ultrasonic horn and bath reactors: effect on structure and preparation of ACE-inhibitory peptides","volume":"20","author":"Zhou","year":"2013","journal-title":"Ultrason Sonochem"},{"key":"2024051611114596000_6.11.e013098.17","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1093\/jn\/117.5.838","article-title":"Beneficial effect of wheat germ on circulating lipoproteins and tissue lipids in rats fed a high fat, cholesterol-containing diet","volume":"117","author":"Lairon","year":"1987","journal-title":"J Nutr"},{"key":"2024051611114596000_6.11.e013098.18","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0271-5317(05)80618-9","article-title":"Effects of increasing levels of raw or defatted wheat germ on liver, feces and plasma lipids and lipoproteins in the rat","volume":"11","author":"Cara","year":"1991","journal-title":"Nutrition Res"},{"key":"2024051611114596000_6.11.e013098.19","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF02194082","article-title":"Plasma lipid lowering effects of wheat germ in hypercholesterolemic subjects","volume":"41","author":"Cara","year":"1991","journal-title":"Plant Foods Hum Nutr"},{"key":"2024051611114596000_6.11.e013098.20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/jn\/122.2.317","article-title":"Long-term wheat germ intake beneficially affects plasma lipids and lipoproteins in hypercholesterolemic human subjects","volume":"122","author":"Cara","year":"1992","journal-title":"J Nutr"},{"key":"2024051611114596000_6.11.e013098.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0740-0020(03)00009-1"},{"key":"2024051611114596000_6.11.e013098.22","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2009.81"},{"key":"2024051611114596000_6.11.e013098.23","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2010.491584"},{"key":"2024051611114596000_6.11.e013098.24","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.8.2261"},{"key":"2024051611114596000_6.11.e013098.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2013.10.010"},{"key":"2024051611114596000_6.11.e013098.26","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health. EFSA Journal 2011;9(12):2474. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/2474 (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2011.2474"},{"key":"2024051611114596000_6.11.e013098.27","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-013-9819-6"},{"key":"2024051611114596000_6.11.e013098.28","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to astaxanthin and maintenance of joints, tendons, and connective tissue (ID 1918, 1978, 3142), protection of DNA, proteins and lipids from oxidative damage (ID 1449, 3141), maintenance of visual acuity (ID 1448), maintenance of blood cholesterol concentrations and maintenance of low plasma concentrations of C-reactive protein (ID 1450) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA Journal 2009; 7(9):1253. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/1253 (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2009.1253"},{"key":"2024051611114596000_6.11.e013098.29","doi-asserted-by":"publisher","DOI":"10.1017\/S0954422410000041"},{"key":"2024051611114596000_6.11.e013098.30","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1017\/S0007114513000032","article-title":"The effect of dietary fibre on reducing the glycaemic index of bread","volume":"109","author":"Scazzina","year":"2013","journal-title":"Br J Nutr"},{"key":"2024051611114596000_6.11.e013098.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.07.050"},{"key":"2024051611114596000_6.11.e013098.32","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.241885"},{"key":"2024051611114596000_6.11.e013098.33","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.29"},{"key":"2024051611114596000_6.11.e013098.34","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e3283218299"},{"key":"2024051611114596000_6.11.e013098.35","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2009.64"},{"key":"2024051611114596000_6.11.e013098.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.09.009"},{"key":"2024051611114596000_6.11.e013098.37","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to decreasing potentially pathogenic gastro-intestinal microorganisms (ID 785) pursuant to Article 13(1) of Regulation (EC) No 1924\/20061. EFSA Journal 2011;9(6):2256. http:\/\/www.efsa.europa.eu\/sites\/default\/files\/scientific_output\/files\/main_documents\/2256.pdf (accessed 15 Sep 2015).","DOI":"10.2903\/j.efsa.2011.2222"},{"key":"2024051611114596000_6.11.e013098.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2010.12.010"},{"key":"2024051611114596000_6.11.e013098.39","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. General scientific guidance for stakeholders on health claim applications. EFSA Journal 2016;14(1):4367. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/4367 (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2016.4367"},{"key":"2024051611114596000_6.11.e013098.40","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Scientific opinion on the substantiation of health claims related to various food(s)\/food constituents(s) and increasing numbers of gastro-intestinal microorganisms (ID 760, 761, 779, 780, 779, 1905), and decreasing potentially pathogenic gastro-intestinal microorganisms (ID 760, 761, 779, 780, 779, 1905) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA Journal 2010;8(10):1809. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/1809 (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2010.1809"},{"key":"2024051611114596000_6.11.e013098.41","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority. Scientific opinion on the substantiation of health claims related to fructo-oligosaccharides (FOS) and decreasing potentially pathogenic gastro-intestinal microorganisms (ID 781) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA Journal 2011;9(6):2222. http:\/\/www.efsa.europa.eu\/en\/efsajournal\/pub\/2222. (accessed 13 Jan 2016).","DOI":"10.2903\/j.efsa.2011.2222"},{"key":"2024051611114596000_6.11.e013098.42","doi-asserted-by":"publisher","DOI":"10.1080\/003655299750025327"},{"key":"2024051611114596000_6.11.e013098.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2005.03.008"},{"key":"2024051611114596000_6.11.e013098.44","unstructured":"Mapi Research Trust. http:\/\/www.mapi-trust.org. (accessed 25 Feb 2015)."},{"key":"2024051611114596000_6.11.e013098.45","doi-asserted-by":"crossref","unstructured":"Wolever TMS . The glycaemic index: a physiological classification of dietary carbohydrate. Oxfordshire: CABI, 2006.","DOI":"10.1079\/9781845930516.0000"},{"key":"2024051611114596000_6.11.e013098.46","doi-asserted-by":"publisher","DOI":"10.1080\/00365520510012208"},{"key":"2024051611114596000_6.11.e013098.47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2009.01408.x"},{"key":"2024051611114596000_6.11.e013098.48","doi-asserted-by":"crossref","first-page":"289","DOI":"10.20452\/pamw.1774","article-title":"Effect of nutrition and atherogenic index on the occurrence and intensity of insulin resistance","volume":"123","author":"Ostrowska","year":"2013","journal-title":"Pol Arch Med Wewn"},{"key":"2024051611114596000_6.11.e013098.49","first-page":"237","article-title":"A avalia\u00e7\u00e3o do stresse: a prop\u00f3sito de um estudo de adapta\u00e7\u00e3o da escala de percep\u00e7\u00e3o de stresse","volume":"10","author":"Pais-Ribeiro","year":"2009","journal-title":"Psicol Sa\u00fade Doen\u00e7as"},{"key":"2024051611114596000_6.11.e013098.50","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1472-6882-10-27","article-title":"An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial","volume":"10","author":"Kuriyan","year":"2010","journal-title":"BMC Complement Altern Med"},{"key":"2024051611114596000_6.11.e013098.51","doi-asserted-by":"publisher","DOI":"10.1177\/1074248411399762"},{"key":"2024051611114596000_6.11.e013098.52","doi-asserted-by":"crossref","first-page":"6390","DOI":"10.3390\/nu7085291","article-title":"Red blood cell docosapentaenoic acid (DPA n-3) is inversely associated with triglycerides and C-reactive protein (CRP) in healthy adults and dose-dependently increases following n-3 fatty acid supplementation","volume":"7","author":"Skulas-Ray","year":"2015","journal-title":"Nutrients"},{"key":"2024051611114596000_6.11.e013098.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2004.09.003"},{"key":"2024051611114596000_6.11.e013098.54","first-page":"620","article-title":"Effect of cooling of cooked white rice on resistant starch content and glycemic response","volume":"24","author":"Sonia","year":"2015","journal-title":"Asia Pac J Clin Nutr"},{"key":"2024051611114596000_6.11.e013098.55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/nmo.12217","article-title":"Effect of prucalopride on symptoms of chronic constipation","volume":"26","author":"Tack","year":"2014","journal-title":"Neurogastroenterol Motil"},{"key":"2024051611114596000_6.11.e013098.56","unstructured":"Pocock SJ . Clinical trials: a practical approach. Chichester, UK: John Wiley & Sons Ltd, 1983."},{"key":"2024051611114596000_6.11.e013098.57","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2009.74"},{"key":"2024051611114596000_6.11.e013098.58","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114511002340"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2016-013098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T13:44:55Z","timestamp":1749735895000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2016-013098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2016,11,10]]},"published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1136\/bmjopen-2016-013098"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2016-013098","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2016,11]]}}}