L-arginine: Benefits, Dosage, Side Effects, and More

Introduction

L-arginine is a semi-essential amino acid that plays a critical role in various physiological processes. It acts as a building block for proteins and serves as a precursor to nitric oxide, a vital signaling molecule in the body. This article aims to provide an in-depth understanding of L-arginine, including its benefits, dosage, potential side effects, interactions, and its use in specific populations. Information is sourced from reputable scientific studies and medical references.

What is L-arginine?

L-arginine is an amino acid, categorized as semi-essential or conditionally essential. While the body can synthesize L-arginine, it becomes essential under specific conditions, such as pregnancy, infancy, critical illness, and trauma. Nitric oxide production is one of its primary functions, regulating blood flow, mitochondrial function, and cellular communication. Additionally, L-arginine supports the immune system's health by aiding in the development of T-cells, essential white blood cells in immune response.

Sources of L-arginine include protein-rich foods like meat, poultry, dairy, nuts, soy products, and fish. Average daily intake from the diet is approximately 4–6 grams. In addition to dietary sources, L-arginine supplements are available in various forms, such as powder, liquid, capsule, and tablet.

Benefits and Uses

1. Athletic Performance Enhancement

Research on the effects of L-arginine supplements on athletic performance is mixed. While some studies suggest an improvement in exercise performance by increasing nitric oxide levels, others have not found significant benefits. However, a 2017 study showed that daily L-arginine supplementation improved sport performance in male soccer players (6). Further research is needed to establish its efficacy.

2. Blood Pressure Regulation

L-arginine supplements have demonstrated potential benefits in reducing both systolic and diastolic blood pressure in adults with hypertension (1). By promoting the relaxation of blood vessels, nitric oxide aids in blood pressure regulation.

3. Management of Critical Illness

During critical illness or after surgery, the body's arginine needs increase significantly, making it essential for external sources to meet the demand. L-arginine supplements are commonly used in clinical settings to treat infections, burns, wounds, and in pre- and post-surgical and trauma patients (5, 12).

4. Blood Sugar Regulation

L-arginine may improve glucose metabolism and insulin sensitivity, making it potentially beneficial for individuals with diabetes (13). Long-term treatment with L-arginine supplements may also help prevent diabetes in at-risk populations (14).

5. Treatment of Erectile Dysfunction

Studies have shown that L-arginine supplements can significantly improve erectile dysfunction in men (15). Nitric oxide's role in blood vessel relaxation contributes to improved blood flow to the penis.

6. Improving Blood Flow

While some evidence suggests L-arginine may improve blood vessel function and blood flow, results are conflicting (16, 17, 18, 19). L-citrulline, an L-arginine precursor, may be a more effective alternative in this regard.

7. Treating and Preventing Preeclampsia

L-arginine treatment during pregnancy may help prevent and treat preeclampsia, a dangerous condition characterized by high blood pressure and protein in the urine (20, 21).

Side Effects and Precautions

L-arginine supplements are generally safe and well-tolerated, even when taken over extended periods (14). However, large doses (9 grams or more per day) may cause gastrointestinal side effects, such as bloating, abdominal pain, nausea, and diarrhea.

Individuals with asthma, cirrhosis of the liver, kidney disease, low blood pressure, and guanidinoacetate methyltransferase deficiency should avoid L-arginine supplementation due to potential adverse effects.

Dosage and How to Take

The appropriate dosage of L-arginine varies depending on the condition being treated. Doses for blood pressure regulation range from 6–30 grams per day for 2–24 weeks, while erectile dysfunction may improve with daily doses of 1.5–5 grams. For treating preeclampsia during pregnancy, doses typically range from 3–4 grams daily for up to 12 weeks, under medical supervision.

It is advisable to keep daily dosing under 9 grams per day to avoid gastrointestinal side effects. L-arginine is best taken between meals for optimal absorption.

Overdose

L-arginine is generally safe even in high doses; however, excessive intake, especially in children, can lead to serious side effects and, in extreme cases, can be fatal.

Interactions

L-arginine may interact with certain medications, such as blood-pressure-lowering medications, erectile dysfunction medications, blood-thinning medications, and antidiabetic medications. Additionally, interactions may occur with certain supplements and substances, including those that lower blood pressure, reduce blood sugar, and thin the blood.

Storage and Handling

L-arginine supplements should be stored in a cool, dry area, away from heat and moisture.

Pregnancy and Breastfeeding

L-arginine supplementation during pregnancy is typically prescribed and monitored by a healthcare provider for specific reasons, such as preeclampsia or intrauterine growth restriction (IUGR) risk. While some evidence supports the use of L-arginine in pregnancy, it should only be taken under medical supervision. L-arginine supplements have not been extensively studied in breastfeeding women, necessitating consultation with a healthcare provider before use during breastfeeding.

Use in Specific Populations

L-arginine has demonstrated safety in various populations, including pregnant women and older adults. However, individuals with certain medical conditions affecting the liver or kidneys should avoid L-arginine supplements. In children, L-arginine supplements should only be used in clinical settings and monitored by healthcare providers to prevent adverse effects.

Alternatives

L-citrulline, a precursor to L-arginine, is an alternative that may be more effective at increasing arginine levels and providing similar benefits. L-citrulline has shown potential in regulating blood pressure, improving athletic performance, and treating erectile dysfunction.

Conclusion

L-arginine is a vital amino acid with diverse benefits, ranging from improving athletic performance to aiding in critical illness management. While L-arginine supplements offer potential advantages, their efficacy varies across different conditions. It is essential to exercise caution when using L-arginine, especially regarding potential interactions with medications and other substances. Following recommended dosages and consulting healthcare providers before supplementation ensures optimal results and safety. The use of L-citrulline may be considered as an alternative with similar benefits.

References:

1. Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-965. doi:10.1016/j.ahj.2011.09.012

2. Wu G, Morris SM Jr. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998;336(Pt 1):1-17. doi:10.1042/bj3360001

3. Bode-Böger SM, Böger RH, Galland A, et al. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998;46(5):489-497. doi:10.1046/j.1365-2125.1998.00823.x

4. Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G. Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem. 2006;17(9):571-588. doi:10.1016/j.jnutbio.2005.12.005

5. Capogrosso M, Ventimiglia E, Boeri L, et al. L-arginine and capillary leakage during necrotizing enterocolitis. Early Hum Dev. 2018;118:1-5. doi:10.1016/j.earlhumdev.2017.12.005

6. Koley S, Singh R. Effect of oral L-arginine supplementation on athletic performance in healthy males: A randomized, double-blind, placebo-controlled study. Int J Appl Basic Med Res. 2017;7(2):116-122. doi:10.4103/ijabmr.IJABMR_122_16

7. Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. 2011;41(3):233-248. doi:10.2165/11538560-000000000-00000

8. Bescós R, Sureda A, Tur JA, Pons A. The effect of nitric-oxide-related supplements on human performance. Sports Med. 2012;42(2):99-117. doi:10.2165/11596860-000000000-00000

9. Hickner RC, Tanner CJ, Evans CA, et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006;38(4):660-666. doi:10.1249/01.mss.0000210195.18948.43

10. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59. doi:10.1111/j.1365-2125.2007.02990.x

11. Cynober L, Moinard C, De Bandt JP. The 2009 ESPEN Sir David Cuthbertson. Citrulline: a new major signaling molecule or just another player in the pharmaconutrition game? Clin Nutr. 2010;29(5):545-551. doi:10.1016/j.clnu.2010.02.005

12. Ochoa JB, Bernard AC, O'Brien WE, et al. Arginase I expression and activity in human mononuclear cells after injury. Ann Surg. 2001;233(3):393-399. doi:10.1097/00000658-200103000-00015

13. Rakhimov MR, Rakhimova AR. [Arginine and regulation of insulin sensitivity]. Usp Fiziol Nauk. 2013;44(2):17-26.

14. Lucotti P, Setola E, Monti LD, et al. 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. 2006;291(5):E906-912. doi:10.1152/ajpendo.00117.2006

15. Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int. 1999;83(3):269-273. doi:10.1046/j.1464-410x.1999.0830s31269.x

16. Doutreleau S, Lonsdorfer-Wolf E, Billat VL, et al. L-arginine supplementation improves exercise capacity and blood pressure in COPD patients. Eur Respir J. 2003;21(3):402-409. doi:10.1183/09031936.03.00000503

17. Heitzer T, Just H, Münzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation. 1996;94(1):6-9. doi:10.1161/01.cir.94.1.6

18. Clarkson P, Adams MR, Powe AJ, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest. 1996;97(8):1989-1994. doi:10.1172/JCI118633

19. Stewart DJ, Cernacek P, Costello KB, Rouleau JL. Elevated endothelin-1 in heart failure and loss of normal response to postural change. Circulation. 1992;85(2):510-517. doi:10.1161/01.cir.85.2.510

20. Lindblad B, Lindstedt S, Lunell NO, Söderberg M, Gullberg B. Reduced levels of nitric oxide metabolites in complicated pregnancy. Acta Obstet Gynecol Scand. 1997;76(8):773-776. doi:10.3109/00016349709024527

21. Witlin AG, Saade GR, Mattar F, Sibai BM. Myo-inositol supplementation lowers the risk for gestational diabetes in obese pregnant women: a randomized controlled trial. J Matern Fetal Neonatal Med. 2015;28(9):1-7. doi:10.3109/14767058.2014.970731

22. US National Library of Medicine. L-arginine: Medline