Abstract
Abstract. L-arginine is an important factor in several physiological and biochemical processes. Recently, scientists studied L-arginine effect on inflammatory mediators such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We conducted a systematic review on randomized controlled trials assessing L-arginine effect on inflammatory mediators. We searched data bases including Google scholar, ISI web of science, SCOPUS, and PubMed/Medline up to April 2019. Randomized clinical trials assessing the effect of L-arginine on inflammatory mediators in human adults were included. Our search retrieved eleven articles with 387 participants. Five articles were on patients with cancer and 6 articles were on adults without cancer. L-arginine was applied in enteral form in 5 articles and in oral form in 6 articles. Eight articles were on both genders, two articles were on women, and one article was on men. L-arginine could not reduce inflammatory mediators among patients with and without cancer except one article which indicated that taking L-arginine for 6 months decreased IL-6 among cardiopathic nondiabetic patients. Our results indicated that L-arginine might not be able to reduce selected inflammatory mediators, but for making a firm decision more studies are needed to be conducted with longer intervention duration, separately on male and female and with different doses of L-arginine.
References
1 (2007) Pharmacokinetics of arginine and related amino acids. J. Nutr. 137, 1646–9.
2 (2004) Arginine pathways and the inflammatory response: interregulation of nitric oxide and polyamines: review article. Amino acids. 26, 321–9.
3 (2004) Nitric oxide mediates protective effect of endothelin receptor antagonism during myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 286, 1767–74.
4 (2005) L-Arginine improves vascular function by overcoming deleterious effects of ADMA, a novel cardiovascular risk factor. Altern Med Rev. 10, 14–23.
5 (2001) Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care. 24, 875–80.
6 (2009) Role of L-arginine in nitric oxide production in health and hypertension. Clin Exp Pharmacol Physiol. 36, 249–55.
7 (2016) Benefits of L-Arginine on Cardiovascular System. Mini Rev Med Chem. 16, 94–103.
8 (2006) Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. 291, E906–12.
9 (2000) Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J Am Coll Cardiol. 35, 706–13.
10 (2017) L-arginine attenuates Interleukin-1beta (IL-1beta) induced Nuclear Factor Kappa-Beta (NF-kappaB) activation in Caco-2 cells. PloS one. 12, e0174441.
11 (2008) Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn’s patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways. J Nutr. 138, 2481–6.
12 (2008) Tumor necrosis factor-alpha downregulates endothelial nitric oxide synthase mRNA stability via translation elongation factor 1-alpha 1. Circ Res. 103, 591–7.
13 (2010) Vascular inflammation in obesity and sleep apnea. Circulation. 121, 1014–21.
14 (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 1813, 878–88.
15 (1998) The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol. 51, 1235–41.
16 (2008) Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial. Nutr Hosp. 23, 105–10.
17 (2014) Effect of L-arginine supplementation on insulin resistance and adipocitokines levels in head and neck cancer non diabetic patients after surgery. Nutr Hosp. 30, 870–5.
18 (2005) Immunoenhanced enteral nutrition, effect on inflammatory markers in head and neck cancer patients. Eur J Clin Nutr. 59, 145–7.
19 (2003) Effect of c-reactive protein and interleukins blood levels in postsurgery arginine-enhanced enteral nutrition in head and neck cancer patients. Eur J Clin Nutr. 57, 96–9.
20 (2001) Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients. Am J Clin Nutr. 73, 323–32.
21 (2012) Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial. Ann Nutr Metab. 60, 157–68.
22 (2000) Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women. J Am Coll Cardiol. 35, 271–6.
23 (2012) Effect of 3-month L-arginine supplementation on insulin resistance and tumor necrosis factor activity in patients with visceral obesity. Eur. Rev Med Pharmacol Sci. 16, 816–23.
24 (2007) Asymmetric dimethylarginine determines the improvement of endothelium-dependent vasodilation by simvastatin: Effect of combination with oral L-arginine. J Am Coll Cardiol. 49, 2274–82.
25 (2009) Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass. Metab Clin Exp. 58, 1270–6.
26 (2005) Oral L-arginine improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men. J Nutr. 135, 212–7.
27 (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 15, e493–503.
28 (2019) Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis. Cancer Manag Res. 11, 6663–80.
29 (2009) High dose of arginine enhanced enteral nutrition in postsurgical head and neck cancer patients. A randomized clinical trial. Eur Rev Med Pharmacol Sci. 13, 279–83.
30 (1999) A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status. JPEN J Parenter Enteral Nutr. 23 (6): 314–20.
31 (1999) Complications of pancreatic surgery and the role of perioperative nutrition. Digsst surg. 16, 320–6.
32 (2000) Postoperative enteral immunonutrition in head and neck cancer patients. Clin Nutr. 19, 407–12.
33 (2001) Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr. 25, 299–308.
34 (1998) Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 42, 431–5.
35 (2000) Modulating effects of the feeding route on stress response and endotoxin translocation in severely stressed patients receiving thoracic esophagectomy. Nutrition. 16, 355–60.
36 (2012) Effect of chronic L-Arginine supplementation on aortic fatty streak formation and serum nitric oxide concentration in normal and high-cholesterol fed rabbits. Acta Physiol Hung. 99, 87–93.
37 (2019) Endothelial dysfunction in dyslipidaemia: Molecular mechanisms and clinical implications. Curr Med Chem.
38 (2007) Effect of arginine on cellular adhesion molecule expression and leukocyte transmigration in endothelial cells stimulated by biological fluid from surgical patients. Shock (Augusta, Ga). 28, 39–44.
39 (2000) Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women. Transl Res. 135 (3): 231–7.
40 (2009) L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. Nutr Res. 29, 291–7.
41 (2009) l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta. Pathophysiology. 16, 9–13.
42 (2018) Association of l-Arginine Supplementation with Markers of Endothelial Function in Patients with Cardiovascular or Metabolic Disorders: A Systematic Review and Meta-Analysis. Nutrients. 11 (1).
43 (2003) Diabetes-induced oxidative stress and low-grade inflammation in porcine coronary arteries. Circulation. 108, 472–8.