What is L-Arginine
L-Arginine is an amino acid made naturally by our bodies and is used in protein biosynthesis. It is also found in foods such as fish, poultry, red meat, and dairy products. L-Arginine is vital to overall health. It is associated with the Krebs Cycle and is a part of the urea cycle where it carries nitrogenous waste. This amino acid also causes vasodilation by its conversion to nitric oxide (NO).1
It is important in maintaining the acid-base balance of the body as the urea cycle is a significant consumer of bicarbonate.
We have recently added this supplement to our product line mostly to be used by athletes. I will cover this, as well as some uses of L-Arginine in this post.
L-Arginine and in vitro fertilization (IVF)
In vitro fertilization has become increasingly popular for couples who struggle to become pregnant. This is often attempted during the later child-bearing years after the woman has failed to become pregnant. There is some research to suggest L-Arginine can increase the number of oocytes collected in women attempting IVF. This, however, has yet to be shown to improve the viable pregnancy rate.2
L-Arginine and Polycystic Ovary Syndrome (PCOS)
A small study of eight patients with polycystic ovary syndrome was published in December of 2009. This study showed that a combination of L-arginine 1600 mg daily combined with N-acetylcysteine 1200 mg daily for a period of six months resulted in moderate improvement of menstrual function and decreased insulin resistance.3
L-Theanine Effects on Cardiovascular Disease and Exercise
L-Arginine may lessen angina symptoms and improve exercise and quality of life in angina patients according to a study published in 2002.4
Another randomized, double-blind cross-over study published in September of 2000, found that, although L-arginine supplementation did not affect exercise-induced changes in QT interval, QT dispersion, or the magnitude of ST segment depression, it significantly improved exercise tolerance. This is most likely the result of improved peripheral vasomotion.5
Many studies have found L-arginine to be effective and decreasing both systolic and diastolic blood pressure. This has been shown in healthy individuals, those with pulmonary hypertension, as well as patients with type 2 diabetes.6
L-arginine also appears to have an additive vasodilation effect when combined with angiotensin converting enzyme (ACE) inhibitors and nitrate vasodilators when used for the treatment of hypertension.10
Intermittent claudication associated with peripheral arterial disease symptoms have also been shown to improve with the administration of oral or intravenous L-arginine for short term periods (up to eight weeks). 15
Although this is promising, walking speed, walking distance, or absolute claudication distance does not seem to improve with long-term (up to six months) administration of L-arginine. 18
L-Arginine and Erectile Dysfunction (ED)
L-arginine has shown some promise in the treatment of erectile dysfunction. A double-blind, placebo-controlled study of 50 men with organic ED showed significant improvement in sexual function in 9/29 (31%) of the treatment group but only 2/17 (11.8%) of the placebo group. The nine patients in the treatment group that showed improvement all had initially low NOx but this level doubled by the end of the study.20
L-arginine seems to be effective in men with mixed-type impotence when combined with Pycogenol at 1.7 grams daily or when combined with both Pycogenol and aspartic acid when dosed at 0.69 grams daily.21
L-Arginine and Statins
The combination of L-arginine and atorvastatin (Lipitor) has been shown to have a significant positive effect on the progression of atherosclerosis. A study utilizing rabbits found this combination to achieve a 21% decrease in the total area of lesions and a 44% reduction in the area of abdominal lesions compared to the control group.23
A two-arm, randomized, double-blind study on 33 hypertriglyceridemic patients reported that L-arginine alone had no effect on serum lipids compared to placebo. When combined with simvastatin, however, led to a significantly larger reduction in triglycerides compared to placebo plus simvastatin. This study also found L-arginine attenuated simvastatin-induced increases in aspartate transaminase and fibrinogen.24
L-Arginine and Body Building
L-arginine is popular with body builders because it helps in the synthesis of proteins. As muscle mass increases, L-arginine helps signal muscle cells and encourages growth hormone release and the metabolism of fat. This leads to a more defined, stronger, well-defined physique. L-arginine can also improve endurance and muscle conditioning due to its vasodilation effects. This increases blood flow to muscle during workout periods.
L-Arginine Drug Interactions
ACE inhibitors, Angiotensin Receptor Blockers (ARBs) and other antihypertensive agents – The combination of L-arginine and ACE inhibitors may lead to increased vasodilation and a larger decrease in blood pressure. When combined, the risk of hypotension exists. Examples include benazepril, captopril, Ramipril, losartan, valsartan, diltiazem, amlodipine, and many more.
Anticoagulants and Antiplatelet Drugs – L-arginine may decrease platelet aggregation in humans. Caution should be exercised when combining L-arginine with medications that increase bleeding risk. Some examples are warfarin, apixaban, rivaroxaban, enoxaparin, clopidigrel, ticlodipine and others.
Isoproterenol and Nitrates – L-arginine may lead to increased vasodilation when combined with vasodilators leading to hypotension and dizziness.
Sildenafil (Viagra) – Although not reported in humans, combining L-Arginine with sildenafil may lead to increased vasodilation and dizziness as well.
Potassium-sparing diuretics – There have been some reports of L-arginine causing hyperkalemia in some patients. Combining L-arginine with these medications may increase the risk of hyperkalemia. Examples of these medications include amiloride, spironolactone, and triamterene.
Adverse Effects of L-Arginine
L-Arginine is generally well tolerated. The most common side effects reported for this supplement are:
- Abdominal pain
- Allergic reactions
- Exacerbation of airway inflammation in asthmatic patients
L-arginine is an amino acid which helps in the synthesis of proteins. It also leads to vasodilation and, in doing so, can be beneficial for relieving chest pain. When combined with a statin, L-arginine leads to a decrease in atherosclerosis which may help prevent heart attacks. It has also been shown to decrease both systolic and diastolic blood pressures. Due to its vasodilation properties, L-arginine may help with the symptoms of erectile dysfunction. It may also help with some of the symptoms of polycystic ovary syndrome when combined with N-acetylcysteine.
We recently added L-arginine as a dietary supplement to our product line with the thought of making it available to body builders. It can increase exercise tolerance and help create a sculpted, muscular body. As it turns out, many other uses are possible with this substance.
L-arginine is relatively safe and well tolerated as it is an amino acid found in the human body. As with any other medication or supplement, allergic reactions are always a possibility. These reactions are often due to fillers and other substances used to produce the dosage form rather than the active chemical. Gastrointestinal side effects are always a possibility as well.
If you have any questions about L-arginine or any other medication or supplement, please feel free to send me an email. I have spent over half of my life working with medications and supplements. As I have expressed in the past, if I do not know the answer to your question, I will find it. Have a great week and live a happy, healthy life. Get plenty of exercise, drink adequate amounts of water, and eat whole foods. You are worth it.
Michael J. Brown, RPh, BCPS, BCPP
Mr. Brown is a Clinical Pharmacist specializing in pharmacotherapy and psychiatry.
Feel free to send Michael a message using this link.
- Tenenbaum A, Fisman EZ, Motro M. L-arginine: Rediscovery in progress. Cardiology 1998;90:153-9.
- Battaglia, C., Salvatori, M., Maxia, N., Petraglia, F., Facchinetti, F., and Volpe, A. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Hum.Reprod. 1999;14(7):1690-1697. View abstract.
- Masha, A., Manieri, C., Dinatale, S., Bruno, G. A., Ghigo, E., and Martina, V. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome. J Endocrinol.Invest 2009;32(11):870-872. View abstract.
- Maxwell AJ, Zapien MP, Pearce GL, MacCallum G, Stone PH. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol. 2002;39(1):37–45. doi:10.1016/s0735-1097(01)01708-9.
- Bednarz B, Wolk R, Chamiec T, Herbaczynska-Cedro K, Winek D, Ceremuzynski L. Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. Int J Cardiol. 2000;75(2-3):205–210. doi:10.1016/s0167-5273(00)00324-7.
- Huynh NT, Tayek JA. Oral arginine reduces systemic blood pressure in type 2 diabetes: its potential role in nitric oxide generation. J Am Coll Nutr. 2002;21(5):422–427. doi:10.1080/07315724.2002.10719245.
- Nagaya N, Uematsu M, Oya H, et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med. 2001;163(4):887–891. doi:10.1164/ajrccm.163.4.2007116.
- Palloshi A, Fragasso G, Piatti P, et al. Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. Am J Cardiol. 2004;93(7):933–935. doi:10.1016/j.amjcard.2003.12.040.
- Ast J, Jablecka A, Bogdanski P, Smolarek I, Krauss H, Chmara E. Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring. Med Sci Monit. 2010;16(5):CR266–CR271.
- Cheng JW, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35:755-64.
- Higashi Y, Oshima T, Sasaki S, et. al. Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension. Hypertension. 1998 Jul;32(1):16-24. View abstract.
- Stokes, G. S., Barin, E. S., Gilfillan, K. L., and Kaesemeyer, W. H. Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave. Am J Hypertens. 2003;16(9 Pt 1):719-724.
- Böger RH, Bode-Böger SM, Thiele W, Creutzig A, Alexander K, Frölich JC. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol. 1998;32(5):1336–1344. doi:10.1016/s0735-1097(98)00375-1.13
14Cheng JW, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35:755-64.
- Maxwell, A. J., Anderson, B. E., and Cooke, J. P. Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar. Vasc.Med. 2000;5(1):11-19.
- Sydow, K., Schwedhelm, E., Arakawa, N., Bode-Boger, S. M., Tsikas, D., Hornig, B., Frolich, J. C., and Boger, R. H. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine and B vitamins. Cardiovasc.Res 2003;57(1):244-252.
- Oka, R. K., Szuba, A., Giacomini, J. C., and Cooke, J. P. A pilot study of L-arginine supplementation on functional capacity in peripheral arterial disease. Vasc.Med. 2005;10(4):265-274.
- Wilson, A. M., Harada, R., Nair, N., Balasubramanian, N., and Cooke, J. P. L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 7-10-2007;116(2):188-195.
- Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. 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 Feb;83(3):269-73. PubMed PMID: 10233492.
- Stanislavov R, Nikolova V. Treatment of erectile dysfunction with Pycnogenol and L-arginine. J Sex Marital Ther 2003;29:207-13.
- Aoki, H., Nagao, J., Ueda, T., Strong, J. M., Schonlau, F., Yu-Jing, S., Lu, Y., and Horie, S. Clinical assessment of a supplement of Pycnogenol(R) and L-arginine in Japanese patients with mild to moderate erectile dysfunction. Phytother.Res. 2012;26(2):204-207.
- Rasmusen C, Moinard C, Martin C, Tricottet V, Cynober L, Couderc R. L-arginine plus atorvastatin for prevention of atheroma formation in genetically hypercholesterolaemic rabbits. Br J Nutr. 2007;97(6):1083–1089. doi:10.1017/S0007114507659066.
- Schulze F, Glos S, Petruschka D, et al. L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. Nutr Res. 2009;29(5):291–297. doi:10.1016/j.nutres.2009.04.004.