l-Citrulline Supplementation: Impact on Cardiometabolic Health

Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO...

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Main Authors: Timothy D. Allerton, David N. Proctor, Jacqueline M. Stephens, Tammy R. Dugas, Guillaume Spielmann, Brian A. Irving
Format: Article
Language:English
Published: MDPI AG 2018-07-01
Series:Nutrients
Subjects:
Online Access:http://www.mdpi.com/2072-6643/10/7/921
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spelling doaj-a0f3881e266d4b52a46d98c9d6cb48ea2020-11-24T22:23:21ZengMDPI AGNutrients2072-66432018-07-0110792110.3390/nu10070921nu10070921l-Citrulline Supplementation: Impact on Cardiometabolic HealthTimothy D. Allerton0David N. Proctor1Jacqueline M. Stephens2Tammy R. Dugas3Guillaume Spielmann4Brian A. Irving5Pennington Biomedical Research Center, Baton Rouge, LA 70808, USADepartment of Kinesiology, Pennsylvania State University, University Park, PA 16802, USAPennington Biomedical Research Center, Baton Rouge, LA 70808, USADepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USAPennington Biomedical Research Center, Baton Rouge, LA 70808, USAPennington Biomedical Research Center, Baton Rouge, LA 70808, USADiminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.http://www.mdpi.com/2072-6643/10/7/921supplementstherapeuticsinterventionswatermelonnitric oxidearginineendothelial functionflow mediated dilationmitochondriaenterocytesliveradipocytesmuscleimmune cellsobesityaginghypertensioninflammationinsulin resistancediabetescardiovascular disease
collection DOAJ
language English
format Article
sources DOAJ
author Timothy D. Allerton
David N. Proctor
Jacqueline M. Stephens
Tammy R. Dugas
Guillaume Spielmann
Brian A. Irving
spellingShingle Timothy D. Allerton
David N. Proctor
Jacqueline M. Stephens
Tammy R. Dugas
Guillaume Spielmann
Brian A. Irving
l-Citrulline Supplementation: Impact on Cardiometabolic Health
Nutrients
supplements
therapeutics
interventions
watermelon
nitric oxide
arginine
endothelial function
flow mediated dilation
mitochondria
enterocytes
liver
adipocytes
muscle
immune cells
obesity
aging
hypertension
inflammation
insulin resistance
diabetes
cardiovascular disease
author_facet Timothy D. Allerton
David N. Proctor
Jacqueline M. Stephens
Tammy R. Dugas
Guillaume Spielmann
Brian A. Irving
author_sort Timothy D. Allerton
title l-Citrulline Supplementation: Impact on Cardiometabolic Health
title_short l-Citrulline Supplementation: Impact on Cardiometabolic Health
title_full l-Citrulline Supplementation: Impact on Cardiometabolic Health
title_fullStr l-Citrulline Supplementation: Impact on Cardiometabolic Health
title_full_unstemmed l-Citrulline Supplementation: Impact on Cardiometabolic Health
title_sort l-citrulline supplementation: impact on cardiometabolic health
publisher MDPI AG
series Nutrients
issn 2072-6643
publishDate 2018-07-01
description Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.
topic supplements
therapeutics
interventions
watermelon
nitric oxide
arginine
endothelial function
flow mediated dilation
mitochondria
enterocytes
liver
adipocytes
muscle
immune cells
obesity
aging
hypertension
inflammation
insulin resistance
diabetes
cardiovascular disease
url http://www.mdpi.com/2072-6643/10/7/921
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