Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use

Maric, Stefano; Muff, Julian; Camargo, Simone M. R.; Guglielmetti, Laura; Holland‐Cunz, Stefan; Crenn, Pascal; Vuille‐dit‐Bille, Raphael N.

doi:10.3390/nu13082794

Cited by 23 publications

(20 citation statements)

References 196 publications

(269 reference statements)

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“…33 Citrulline level of 40 ±10 µmol/L is considered normal. 32 The abnormal citrulline levels in our population may indirectly suggest intestinal epithelial damage. However, several other factors need to be considered when interpreting these results.…”

Section: Discussionmentioning

confidence: 85%

“…13 The usefulness of citrulline for the direct functional assessment of enterocyte mass has been confirmed in previous research studies. 16,32 According to the literature, citrulline cutoff values have a sensitivity of 80% and a specificity of 84% for diagnosing intestinal dysfunction. The most commonly used threshold for low citrulline levels is 20 µmol/L, 16 which is in line with our findings.…”

Section: Discussionmentioning

confidence: 99%

“…According to other investigators, a citrulline threshold of 10 µmol/L indicates a significant loss of enterocyte mass. 32 Finally, it has been reported that citrulline levels ranging from 10 µmol/L to 20 µmol/L are a grey zone for interpretation in critically ill patients. 33 Citrulline level of 40 ±10 µmol/L is considered normal.…”

Section: Discussionmentioning

confidence: 99%

“…This is surprising because kidney disorders and enhanced inflammatory processes may induce changes in citrulline levels. 32 Citrulline is converted to arginine in the kidneys. Arginine is then used in nitric oxide synthesis, for example, in response to inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Citrulline and long-term mortality in patients with cardiovascular disease

Konieczny¹,

Żurawska-Płaksej²,

Kaaz³

et al. 2022

Adv Clin Exp Med

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Background. Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD. Objectives.To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers -citrulline and TMAO -was assessed.Materials and methods. Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed. Results. The median citrulline level in the study population was 22.5 µM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027).Conclusions. Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Citrulline and long-term mortality in patients with cardiovascular disease

Konieczny¹,

Żurawska-Płaksej²,

Kaaz³

et al. 2022

Adv Clin Exp Med

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“…Furthermore, transporter expression does not necessarily reflect absorption. While some transporters have been shown to functionally interact [ 26 , 27 , 28 , 29 ], others depend on the presence of certain accessory proteins (e.g., angiotensin converting enzyme 2 (ACE2)) [ 22 , 25 , 30 ]. Expression of some transport proteins such as GLUT2 and SGLT1 is comparable between the newborn and adult small intestine.…”

Section: Introductionmentioning

confidence: 99%

Surgical Treatment of Short Bowel Syndrome—The Past, the Present and the Future, a Descriptive Review of the Literature

et al. 2022

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Short bowel syndrome (SBS) is a devastating disorder with both short- and long-term implications for patients. Unfortunately, the prevalence of SBS has doubled over the past 40 years. Broadly speaking, the etiology of SBS can be categorized as congenital or secondary, the latter typically due to extensive small bowel resection following diseases of the small intestine, e.g., necrotizing enterocolitis, Hirschsprung’s disease or intestinal atresia. As of yet, no cure exists, thus, conservative treatment, primarily parenteral nutrition (PN), is the first-line therapy. In some cases, weaning from PN is not possible and operative therapy is required. The invention of the longitudinal intestinal lengthening and tailoring (LILT or Bianchi) procedure in 1980 was a major step forward in patient care and spawned further techniques that continue to improve lives for patients with severe SBS (e.g., double barrel enteroplasty, serial transverse enteroplasty, etc.). With this review, we aim to provide an overview of the clinical implications of SBS, common conservative therapies and the development of operative techniques over the past six decades. We also provide a short outlook on the future of operative techniques, specifically with respect to regenerative medicine.

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L‐Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload

Zhao,

Gao,

Chen

et al. 2024

Molecular Nutrition Food Res

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ScopeOxidative stress caused by iron overload tends to result in intestinal mucosal barrier dysfunction and intestinal microbiota imbalance. As a neutral and nonprotein amino acid, L‐Citrulline (L‐cit) has been implicated in antioxidant and mitochondrial amelioration properties. This study investigates whether L‐cit can alleviate iron overload‐induced intestinal injury and explores the underlying mechanisms.Methods and resultsC57BL/6J mice are intraperitoneally injected with iron dextran, then gavaged with different dose of L‐cit for 2 weeks. L‐cit treatment significantly alleviates intestine pathological injury, oxidative stress, ATP level, and mitochondrial respiratory chain complex activities, accompanied by ameliorating mitochondrial quality control. L‐cit‐mediated protection is associated with the upregulation of Glutathione Peroxidase 4 (GPX4) expression, inhibition Nuclear Receptor Coactivator 4 (NCOA4)‐mediated ferritinophagy and ferroptosis, and improvement of gut microbiota. To investigate the underlying molecular mechanisms, Intestinal Porcine Epithelial Cell line‐J2 (IPEC‐J2) cells are treated with L‐cit or AMP‐activated Protein Kinase (AMPK) inhibitor. AMPK signaling has been activated by L‐cit. Notably, Compound C abolishes L‐cit's protection on intestinal barrier, mitochondrial function, and antioxidative capacity in IPEC‐J2 cells.ConclusionL‐cit may restrain ferritinophagy and ferroptosis to regulate iron metabolism, and induce AMPK pathway activation, which contributes to exert antioxidation, ameliorate iron metabolism and mitochondrial quality control, and improve intestinal microbiota. L‐cit is a promising therapeutic strategy for iron overload‐induced intestinal injury.

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Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use

Cited by 23 publications

References 196 publications

Citrulline and long-term mortality in patients with cardiovascular disease

Citrulline and long-term mortality in patients with cardiovascular disease

Surgical Treatment of Short Bowel Syndrome—The Past, the Present and the Future, a Descriptive Review of the Literature

L‐Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload

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