{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:59:20Z","timestamp":1791572360163,"version":"4.3.4"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Zealand Ministry of Business, Innovation and Employment","award":["IRSES-318962-BIOAGE"],"award-info":[{"award-number":["IRSES-318962-BIOAGE"]}]},{"DOI":"10.13039\/501100003524","name":"Ministry of Business, Innovation and Employment","doi-asserted-by":"publisher","award":["RSES-318962-BIOAGE"],"award-info":[{"award-number":["RSES-318962-BIOAGE"]}],"id":[{"id":"10.13039\/501100003524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Higher dietary protein intake is increasingly recommended for the elderly; however, high protein diets have also been linked to increased cardiovascular disease (CVD) risk. Trimethylamine-N-oxide (TMAO) is a bacterial metabolite derived from choline and carnitine abundant from animal protein-rich foods. TMAO may be a novel biomarker for heightened CVD risk. The purpose of this study was to assess the impact of a high protein diet on TMAO. Healthy men (74.2 \u00b1 3.6 years, n = 29) were randomised to consume the recommended dietary allowance of protein (RDA: 0.8 g protein\/kg bodyweight\/day) or twice the RDA (2RDA) as part of a supplied diet for 10 weeks. Fasting blood samples were collected pre- and post-intervention for measurement of TMAO, blood lipids, glucose tolerance, insulin sensitivity, and inflammatory biomarkers. An oral glucose tolerance test was also performed. In comparison with RDA, the 2RDA diet increased circulatory TMAO (p = 0.002) but unexpectedly decreased renal excretion of TMAO (p = 0.003). LDL cholesterol was increased in 2RDA compared to RDA (p = 0.049), but no differences in other biomarkers of CVD risk and insulin sensitivity were evident between groups. In conclusion, circulatory TMAO is responsive to changes in dietary protein intake in older healthy males.<\/jats:p>","DOI":"10.3390\/nu11092207","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T10:56:06Z","timestamp":1568285766000},"page":"2207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO)"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-969X","authenticated-orcid":false,"given":"Sarah M.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-7326","authenticated-orcid":false,"given":"Amber M.","family":"Milan","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"},{"name":"Food Nutrition &amp; Health Team, Food &amp; Bio-based Products Group, AgResearch, Palmerston North 4442, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-6806","authenticated-orcid":false,"given":"Cameron J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"},{"name":"School of Kinesiology, University of British Columbia, Vancouver, BC V6T 1Z1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola A.","family":"Gillies","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall F.","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"},{"name":"Discipline of Nutrition, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-8321","authenticated-orcid":false,"given":"Nina","family":"Zeng","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-1282","authenticated-orcid":false,"given":"Farha","family":"Ramzan","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-8585","authenticated-orcid":false,"given":"Pankaja","family":"Sharma","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-5513","authenticated-orcid":false,"given":"Scott O.","family":"Knowles","sequence":"additional","affiliation":[{"name":"Food Nutrition &amp; Health Team, Food &amp; Bio-based Products Group, AgResearch, Palmerston North 4442, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-9705","authenticated-orcid":false,"given":"Nicole C.","family":"Roy","sequence":"additional","affiliation":[{"name":"Food Nutrition &amp; Health Team, Food &amp; Bio-based Products Group, AgResearch, Palmerston North 4442, New Zealand"},{"name":"Riddet Institute, Massey University, Palmerston North 4442, New Zealand"},{"name":"The High-Value Nutrition National Science Challenge, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Sj\u00f6din","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Exercise and Sport, Copenhagen University, 1165 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Research Platform Active Ageing, University of Vienna, 1010 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Zeisel","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute, University of North Carolina, Kannapolis, NC 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-5816","authenticated-orcid":false,"given":"David","family":"Cameron-Smith","sequence":"additional","affiliation":[{"name":"Liggins Institute, The University of Auckland, Auckland 1023, New Zealand"},{"name":"Riddet Institute, Massey University, Palmerston North 4442, New Zealand"},{"name":"Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.jamda.2013.05.021","article-title":"Evidence-based recommendations for optimal dietary protein intake in older people: A position paper from the PROT-AGE Study Group","volume":"14","author":"Bauer","year":"2013","journal-title":"J. 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