Skip to main content Accessibility help

The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials

  • Amir Hadi (a1), Arman Arab (a2), Sajjad Moradi (a3), Ana Pantovic (a4), Cain C. T. Clark (a5) and Ehsan Ghaedi (a6) (a7)...


A number of clinical trials have examined the effect of l-arginine on lipid profile in recent years; however, the results remain equivocal. Therefore, the present study aims to summarise and quantitatively examine the available evidence on the effectiveness l-arginine supplementation on lipid parameters using a systematic review and meta-analytic approach. Online databases including PubMed, Scopus, ISI Web of Science, Cochrane Library and Google Scholar were searched up to April 2019 for randomised controlled trials that examined the effect of l-arginine supplementation on lipid profile in adults. Treatment effects were expressed as weighted mean difference (WMD) and the corresponding standard error in concentrations of serum lipids. To estimate the overall effect of l-arginine supplementation, we used the random-effects model. In total, twelve studies were included in the systematic review. The meta-analysis revealed that l-arginine supplementation did not significantly change the concentrations of total cholesterol (WMD: –5·03 mg/dl; 95 % CI –10·78, 0·73; P = 0·08; inconsistency index (I2) = 39·0 %), LDL (WMD: –0·47 mg/dl; 95 % CI –3·61, 2·66; P = 0·76; I2 = 0·0 %), or HDL (WMD: 0·57 mg/dl; 95 % CI –1·28, 2·43; P = 0·54; I2 = 68·4 %). A significant reduction was observed only in serum TAG levels (WMD: –7·04 mg/dl; 95 % CI –11·42, –2·67; P < 0·001; I2 = 0·0 %). This meta-analysis concludes that l-arginine supplementation can significantly reduce blood TAG levels; however, there is insufficient evidence to support its hypocholesterolaemic effects. To draw straightforward conclusions regarding generalised recommendations for l-arginine supplementation for improving lipid profile, there is a need for more well-controlled trials targeting exclusively patients with dyslipidaemia.


Corresponding author

*Corresponding author: E. Ghaedi, email


Hide All
1.Yusuf, S, Reddy, S, Ôunpuu, S, et al. (2001) Global burden of cardiovascular diseases: Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 104, 28552864.
2.Leal, J, Luengo-Fernández, R, Gray, A, et al. (2006) Economic burden of cardiovascular diseases in the enlarged European Union. Eur Heart J 27, 16101619.
3.Mozaffarian, D, Benjamin, EJ, Go, AS, et al. (2016) Heart disease and stroke statistics – 2016 update: a report from the American Heart Association. Circulation 133, e38–e360.
4.Rader, DJ (2007) Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am J Med 120, S12S18.
5.Lehto, S, Rönnemaa, T, Haffher, SM, et al. (1997) Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM. Diabetes 46, 13541359.
6.McPherson, R, Frohlich, J, Fodor, G, et al. (2006) Canadian Cardiovascular Society position statement – recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol 22, 913927.
7.Ito, MK (2012) Dyslipidemia: management using optimal lipid-lowering therapy. Ann Pharmacother 46, 13681381.
8.Chang, Y & Robidoux, J (2017) Dyslipidemia management update. Curr Opin Pharmacol 33, 4755.
9.Björnsson, ES (2017) Hepatotoxicity of statins and other lipid-lowering agents. Liver Int 37, 173178.
10.Padala, S & Thompson, PD (2012) Statins as a possible cause of inflammatory and necrotizing myopathies. Atherosclerosis 222, 1521.
11.Chalasani, N (2005) Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 41, 690695.
12.McNeal, CJ, Meininger, CJ, Reddy, D, et al. (2016) Safety and effectiveness of arginine in adults. J Nutr 146, 2587S2593S.
13.Ástvaldsdóttir, Á, Naimi-Akbar, A, Davidson, T, et al. (2016) Arginine and caries prevention: a systematic review. Caries Res 50, 383393.
14.McRae, MP (2016) Therapeutic benefits of L-arginine: an umbrella review of meta-analyses. J Chiropractic Med 15, 184189.
15.Stechmiller, JK, Childress, B & Cowan, L (2005) Arginine supplementation and wound healing. Nutr Clin Prac 20, 5261.
16.Popovic, PJ, Zeh, III HJ & Ochoa, JB (2007) Arginine and immunity. J Nutr 137, 1681S1686S.
17.Rodrigues-Krause, J, Krause, M, Rocha, I, et al. (2019) 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, 15.
18.Suliburska, J, Bogdanski, P, Szulinska, M, et al. (2014) Changes in mineral status are associated with improvements in insulin sensitivity in obese patients following L-arginine supplementation. Eur J Nutr 53, 387393.
19.McRae, MP (2016) Therapeutic benefits of L-arginine: an umbrella review of meta-analyses. J Chiropr Med 15, 184189.
20.Dashtabi, A, Mazloom, Z, Fararouei, M, et al. (2015) Oral L-arginine administration improves anthropometric and biochemical indices associated with cardiovascular diseases in obese patients: a randomized, single blind placebo controlled clinical trial. Res Cardiovasc Med 5, e29419.
21.Pahlavani, N, Jafari, M, Sadeghi, O, et al. (2014) L-Arginine supplementation and risk factors of cardiovascular diseases in healthy men: a double-blind randomized clinical trial. F1000Res 3, 306.
22.Rahimi, M & Naghizadeh, MM (2014) The effect of L-arginin supplementation on lipid profiles in patients with diabetes type 2. J Fasa Univ Med Sci 4, 99110.
23.Bahrami, D, Mozaffari-Khosravi, H & Zavar-Reza, J (2019) The effect of oral L-arginine supplementation on lipid profile, glycemic status, and insulin resistance in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial. Mediterranean J Nutr Metab 12, 7990.
24.Bogdanski, P, Suliburska, J, Grabanska, K, et al. (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, 816823.
25.Schulze, F, Glos, S, Petruschka, D, et al. (2009) L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. Nutr Res 29, 291297.
26.Lucotti, P, Monti, L, Setola, E, et al. (2009) Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass. Metabolism 58, 12701276.
27.Monti, LD, Galluccio, E, Villa, V, et al. (2018) Decreased diabetes risk over 9 year after 18-month oral L-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of L-arginine study). Eur J Nutr 57, 28052817.
28.Blum, A, Cannon, III RO, Costello, R, et al. (2000) Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women. J Lab Clin Med 135, 231237.
29.Pourghassem Gargari, B, Alizadeh, M, Safaeiyan, A, et al. (2015) Effect of L-arginine and selenium on metabolic features, insulin resistance and hepatic function tests in obese women. Curr Nutr Food Sci 11, 9398.
30.Clarkson, P, Adams, MR, Powe, AJ, et al. (1996) Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 97, 19891994.
31.Moher, D, Liberati, A, Tetzlaff, J, et al. (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Internal Med 151, 264269.
32.Higgins, J & Green, S (2014) Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration. Chichester: John Wiley & Sons Ltd.
33.DerSimonian, R & Laird, N (1986) Meta-analysis in clinical trials. Control Clin Trials 7, 177188.
34.Begg, CB & Mazumdar, M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 10881101.
35.Egger, M, Smith, GD, Schneider, M, et al. (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629634.
36.Wascher, TC, Graier, WF, Dittrich, P, et al. (1997) Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity. Eur J Clin Invest 27, 690695.
37.Natarajan Sulochana, K, Lakshmi, S, Punitham, R, et al. (2002) Effect of oral supplementation of free amino acids in type 2 diabetic patients – a pilot clinical trial. Med Sci Monit 8, Cr131–Cr137.
38.Grundy, SM (1999) Hypertriglyceridemia, insulin resistance, and the metabolic syndrome. Am J Cardiol 83, 2529.
39.Ginsberg, HN (2000) Insulin resistance and cardiovascular disease. J Clin Invest 106, 453458.
40.Wu, Z, Satterfield, MC, Bazer, FW, et al. (2012) Regulation of brown adipose tissue development and white fat reduction by L-arginine. Curr Opin Clin Nutr Metab Care 15, 529538.
41.Paolisso, G, Tagliamonte, MR, Marfella, R, et al. (1997) L-Arginine but not D-arginine stimulates insulin-mediated glucose uptake. Metabolism 46, 10681073.
42.Li, X, Bazer, FW, Gao, H, et al. (2009) Amino acids and gaseous signaling. Amino Acids 37, 6578.
43.Forstermann, U & Sessa, WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33, 829837, 837a–837d.
44.Ricart-Jane, D, Casanovas, A, Jane, N, et al. (2008) Nitric oxide and the release of lipoprotein lipase from white adipose tissue. Cell Physiol Biochem 22, 525530.
45.Mendez, J & Balderas, F (2001) Regulation of hyperglycemia and dyslipidemia by exogenous L-arginine in diabetic rats. Biochimie 83, 453458. Castro Barbosa, T, Jiang, LQ, Zierath, JR, et al. (2013) L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO/c-GMP pathway. Metabolism 62, 7989.
47.El-Kirsh, AAA, Abd El-Wahab, HMF & Abd-Ellah Sayed, HF (2011) The effect of L-arginine or L-citrulline supplementation on biochemical parameters and the vascular aortic wall in high-fat and high-cholesterol-fed rats. Cell Biochem Func 29, 414428.
48.Emadi, M, Jahanshiri, F, Kaveh, K, et al. (2011) Nutrition and immunity: the effects of the combination of arginine and tryptophan on growth performance, serum parameters and immune response in broiler chickens challenged with infectious bursal disease vaccine. Avian Pathol 40, 6372.
49.Kumar, P, Kumar, A & Tiwari, S (2005) L-Arginine supplementation increases serum cholesterol level. Indian J Pharmacol 37, 183.
50.dos Santos Madeira, MSM, Rolo, ESA, Pires, VMR, et al. (2017) Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine. BMC Vet Res 13, 145.
51.Hu, S, Li, X, Rezaei, R, et al. (2015) Safety of long-term dietary supplementation with L-arginine in pigs. Amino Acids 47, 925936.
52.He, Q, Kong, X, Wu, G, et al. (2009) Metabolomic analysis of the response of growing pigs to dietary L-arginine supplementation. Amino Acids 37, 199.
53.Fouad, A, El-Senousey, H, Yang, X, et al. (2013) Dietary L-arginine supplementation reduces abdominal fat content by modulating lipid metabolism in broiler chickens. Animal 7, 12391245.
54.Madeira, M, Alfaia, C, Costa, P, et al. (2014) The combination of arginine and leucine supplementation of reduced crude protein diets for boars increases eating quality of pork. J Anim Sci 92, 20302040.
55.Tan, B, Yin, Y, Liu, Z, et al. (2011) Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle. J Nutr Biochem 22, 441445.
56.Harisa, G (2011) L-Arginine ameliorates arylesterase/paraoxonase activity of paraoxonase 1 in hypercholesterolemic rats. Asian J Biochem 6, 263272.
57.Böger, RH & Bode-Böger, SM (2001) The clinical pharmacology of L-arginine. Ann Rev Pharmacol Toxicol 41, 7999.
58.Böger, RH (2014) The pharmacodynamics of L-arginine. Altern Therap Health Med 20, 4854.
59.Utagawa, T (2004) Arginine metabolism: enzymology, nutrition, and clinical significance. J Nutr 134, 2854S2857S.
60.Morris, SM Jr (2007) Arginine metabolism: boundaries of our knowledge. J Nutr 137, 1602S1609S.


The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials

  • Amir Hadi (a1), Arman Arab (a2), Sajjad Moradi (a3), Ana Pantovic (a4), Cain C. T. Clark (a5) and Ehsan Ghaedi (a6) (a7)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed