Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study
As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulli...
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| Veröffentlicht in: | Clinical nutrition (Edinburgh, Scotland) Scotland), 2019-12, Vol.38 (6), p.2599-2606 |
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| creator | Jirka, Adam Layec, Sabrina Picot, Denis Bernon-Ferreira, Silvia Grasset, Nadège Flet, Laurent Thibault, Ronan Darmaun, Dominique |
| description | As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulline impacts whole body protein metabolism in patients with SBS.
Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1–13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen.
Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 μmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p |
| doi_str_mv | 10.1016/j.clnu.2018.12.030 |
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Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1–13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen.
Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 μmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p < 4 × 10−6). Supplementation did not alter leucine appearance rate (97 ± 5 vs. 97 ± 5 μmol kg−1.h−1; p = 0.88), leucine oxidation (14 ± 1 vs. 12 ± 1 μmol kg−1.h−1; p = 0.22), or non-oxidative leucine disposal (NOLD), an index of whole-body protein synthesis (83 ± 4 vs. 85 ± 5 μmol kg−1.h−1; p = 0.36), nor insulin or IGF-1 plasma concentrations. In each of the 3 patients with baseline citrulline<20 μmol/L, citrulline supplementation increased NOLD. Among the 7 patients with plasma citrulline <30 μmol/L, the effect of supplementation on NOLD correlated inversely (r2 = 0.81) with baseline plasma citrulline concentration.
1) Oral citrulline supplementation enhances citrulline and arginine bioavailability in SBS patients. 2) Oral citrulline supplementation does not have any anabolic effect on whole body protein metabolism in patients with SBS in good nutritional status, in the late phase of intestinal adaptation, and with near-normal baseline citrulline homeostasis. 3) Whether oral citrulline would impact whole body protein anabolism in severely malnourished SBS patients in the early adaptive period, and with baseline plasma citrulline below 20 μmol/L, warrants further study. Registered under ClinicalTrials.gov Identifier no. NCT01386034.</description><identifier>ISSN: 0261-5614</identifier><identifier>ISSN: 2405-4577</identifier><identifier>EISSN: 1532-1983</identifier><identifier>EISSN: 2405-4577</identifier><identifier>DOI: 10.1016/j.clnu.2018.12.030</identifier><identifier>PMID: 30642738</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amino acids ; Arginine ; Endocrinology and metabolism ; Food and Nutrition ; Human health and pathology ; Intestinal deficiency ; Life Sciences ; Stable isotopes</subject><ispartof>Clinical nutrition (Edinburgh, Scotland), 2019-12, Vol.38 (6), p.2599-2606</ispartof><rights>2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism</rights><rights>Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-f86771ed456e4ca5f7eab06921595efd1cb3e97024edc427866a642dfd1035b03</citedby><cites>FETCH-LOGICAL-c434t-f86771ed456e4ca5f7eab06921595efd1cb3e97024edc427866a642dfd1035b03</cites><orcidid>0000-0002-6038-5649</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0261561418325986$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30642738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://univ-rennes.hal.science/hal-02020471$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Jirka, Adam</creatorcontrib><creatorcontrib>Layec, Sabrina</creatorcontrib><creatorcontrib>Picot, Denis</creatorcontrib><creatorcontrib>Bernon-Ferreira, Silvia</creatorcontrib><creatorcontrib>Grasset, Nadège</creatorcontrib><creatorcontrib>Flet, Laurent</creatorcontrib><creatorcontrib>Thibault, Ronan</creatorcontrib><creatorcontrib>Darmaun, Dominique</creatorcontrib><title>Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study</title><title>Clinical nutrition (Edinburgh, Scotland)</title><addtitle>Clin Nutr</addtitle><description>As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulline impacts whole body protein metabolism in patients with SBS.
Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1–13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen.
Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 μmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p < 4 × 10−6). Supplementation did not alter leucine appearance rate (97 ± 5 vs. 97 ± 5 μmol kg−1.h−1; p = 0.88), leucine oxidation (14 ± 1 vs. 12 ± 1 μmol kg−1.h−1; p = 0.22), or non-oxidative leucine disposal (NOLD), an index of whole-body protein synthesis (83 ± 4 vs. 85 ± 5 μmol kg−1.h−1; p = 0.36), nor insulin or IGF-1 plasma concentrations. In each of the 3 patients with baseline citrulline<20 μmol/L, citrulline supplementation increased NOLD. Among the 7 patients with plasma citrulline <30 μmol/L, the effect of supplementation on NOLD correlated inversely (r2 = 0.81) with baseline plasma citrulline concentration.
1) Oral citrulline supplementation enhances citrulline and arginine bioavailability in SBS patients. 2) Oral citrulline supplementation does not have any anabolic effect on whole body protein metabolism in patients with SBS in good nutritional status, in the late phase of intestinal adaptation, and with near-normal baseline citrulline homeostasis. 3) Whether oral citrulline would impact whole body protein anabolism in severely malnourished SBS patients in the early adaptive period, and with baseline plasma citrulline below 20 μmol/L, warrants further study. Registered under ClinicalTrials.gov Identifier no. NCT01386034.</description><subject>Amino acids</subject><subject>Arginine</subject><subject>Endocrinology and metabolism</subject><subject>Food and Nutrition</subject><subject>Human health and pathology</subject><subject>Intestinal deficiency</subject><subject>Life Sciences</subject><subject>Stable isotopes</subject><issn>0261-5614</issn><issn>2405-4577</issn><issn>1532-1983</issn><issn>2405-4577</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kd-K1DAYxYso7rj6Al5ILhW2NX_atCN7MyyrKwx4o9chTb4yGdKmJukM4yv5kn7jrHspCYQkv3NCzimKt4xWjDL5cV8ZPy0Vp6yrGK-ooM-KFWsEL9m6E8-LFeWSlY1k9VXxKqU9pbQRbfeyuBJU1rwV3ar4fT8MYDIJAwlRe2Jcjov3bgKSlnn2MMKUdXZhIjiPu-CB9MGeyBxDBjeREbLug3dpJLjTdvGZzChAWSJHl3ck7ULMKDqCJ-k02RhG-EQ2ZHY-5BsS9WTD6H6BvSE2LL2Hssf3cWdiSKkMB4gk5cWeXhcvBu0TvHlcr4sfn--_3z2U229fvt5ttqWpRZ3LoZNty8DWjYTa6GZoQfdUrjlr1g0MlplewLqlvAZrMIZOSo1xWLyhoumpuC4-XHx32qs5ulHHkwraqYfNVp3PKMdRt-zAkH1_YTGPnwukrEaXDHivJwhLUpy1ayEaJiWi_IL-_VeE4cmbUXUuVO3VuVB1LlQxrrBQFL179F_6EeyT5F-DCNxeAMBEDg6iSgbDN2BdxGKVDe5__n8At6W02g</recordid><startdate>201912</startdate><enddate>201912</enddate><creator>Jirka, Adam</creator><creator>Layec, Sabrina</creator><creator>Picot, Denis</creator><creator>Bernon-Ferreira, Silvia</creator><creator>Grasset, Nadège</creator><creator>Flet, Laurent</creator><creator>Thibault, Ronan</creator><creator>Darmaun, Dominique</creator><general>Elsevier Ltd</general><general>ESPEN/Elsevier</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-6038-5649</orcidid></search><sort><creationdate>201912</creationdate><title>Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study</title><author>Jirka, Adam ; Layec, Sabrina ; Picot, Denis ; Bernon-Ferreira, Silvia ; Grasset, Nadège ; Flet, Laurent ; Thibault, Ronan ; Darmaun, Dominique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-f86771ed456e4ca5f7eab06921595efd1cb3e97024edc427866a642dfd1035b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Amino acids</topic><topic>Arginine</topic><topic>Endocrinology and metabolism</topic><topic>Food and Nutrition</topic><topic>Human health and pathology</topic><topic>Intestinal deficiency</topic><topic>Life Sciences</topic><topic>Stable isotopes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jirka, Adam</creatorcontrib><creatorcontrib>Layec, Sabrina</creatorcontrib><creatorcontrib>Picot, Denis</creatorcontrib><creatorcontrib>Bernon-Ferreira, Silvia</creatorcontrib><creatorcontrib>Grasset, Nadège</creatorcontrib><creatorcontrib>Flet, Laurent</creatorcontrib><creatorcontrib>Thibault, Ronan</creatorcontrib><creatorcontrib>Darmaun, Dominique</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jirka, Adam</au><au>Layec, Sabrina</au><au>Picot, Denis</au><au>Bernon-Ferreira, Silvia</au><au>Grasset, Nadège</au><au>Flet, Laurent</au><au>Thibault, Ronan</au><au>Darmaun, Dominique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study</atitle><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle><addtitle>Clin Nutr</addtitle><date>2019-12</date><risdate>2019</risdate><volume>38</volume><issue>6</issue><spage>2599</spage><epage>2606</epage><pages>2599-2606</pages><issn>0261-5614</issn><issn>2405-4577</issn><eissn>1532-1983</eissn><eissn>2405-4577</eissn><abstract>As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulline impacts whole body protein metabolism in patients with SBS.
Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1–13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen.
Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 μmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p < 4 × 10−6). Supplementation did not alter leucine appearance rate (97 ± 5 vs. 97 ± 5 μmol kg−1.h−1; p = 0.88), leucine oxidation (14 ± 1 vs. 12 ± 1 μmol kg−1.h−1; p = 0.22), or non-oxidative leucine disposal (NOLD), an index of whole-body protein synthesis (83 ± 4 vs. 85 ± 5 μmol kg−1.h−1; p = 0.36), nor insulin or IGF-1 plasma concentrations. In each of the 3 patients with baseline citrulline<20 μmol/L, citrulline supplementation increased NOLD. Among the 7 patients with plasma citrulline <30 μmol/L, the effect of supplementation on NOLD correlated inversely (r2 = 0.81) with baseline plasma citrulline concentration.
1) Oral citrulline supplementation enhances citrulline and arginine bioavailability in SBS patients. 2) Oral citrulline supplementation does not have any anabolic effect on whole body protein metabolism in patients with SBS in good nutritional status, in the late phase of intestinal adaptation, and with near-normal baseline citrulline homeostasis. 3) Whether oral citrulline would impact whole body protein anabolism in severely malnourished SBS patients in the early adaptive period, and with baseline plasma citrulline below 20 μmol/L, warrants further study. Registered under ClinicalTrials.gov Identifier no. NCT01386034.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30642738</pmid><doi>10.1016/j.clnu.2018.12.030</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-6038-5649</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elsevier ScienceDirect Journals; Alma/SFX Local Collection |
| subjects | Amino acids Arginine Endocrinology and metabolism Food and Nutrition Human health and pathology Intestinal deficiency Life Sciences Stable isotopes |
| title | Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study |
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