Scientific studies show the combination of L-Citrulline and L-Arginine increases Nitric Oxide production for cardiovascular, immune boosting, and sexual health benefits!
This article is a repost which originally appeared on US Smart Publications
You have probably heard of the amino acid L-arginine, which is also called simply arginine.It is well known in the nutrition science community for its ability to increase nitric oxide production resulting in a wide variety of health benefits. But you probably have not heard much about its powerful amino acid cousin, L-citrulline, or just citrulline.If you eat at least six cups of watermelon every day then you’re getting an adequate dose of the amino acid citrulline. Citrulline’s name is actually derived from the Latin word for watermelon—citrullus—because it was first isolated from the fruit in 1930.1
What does L-Citrulline and L-Arginine do?
Together they help:
– Support cardiovascular health by boosting nitric oxide production and helping blood flow more easily throughout the body
– Support healthy blood pressure and boost the immune system
– Detoxify the liver and eliminate ammonia from the body
– Improve sexual stamina and enhance recovery from an intense workout
Who might benefit from taking a supplement containing
both citrulline and arginine?
– Anyone who wants to support healthy blood pressure Individuals who want to avoid angina (chest pain)
– Individuals who want to avoid leg pain due to poor blood circulation
– Anyone who wants protection from heart attack and stroke
– Men suffering from erectile dysfunction
– Athletes who want a faster recovery
How are citrulline and arginine related?
As soon as citrulline enters the kidney, vascular endothelium and other tissues, it is converted into arginine. Plasma and tissue levels of arginine increase, which is necessary for the production of nitric oxide and relaxation of blood vessels. An additional benefit of supplemental citrulline is that it helps eliminate ammonia, a highly toxic substance, from the liver.
Will citrulline and arginine help my sex life?
The answer is yes. Arginine has been well studied for its ability to enhance sexual satisfaction. Both men and women report longer and more intense orgasms when their intake of arginine increases. Additionally, arginine is often used by men to achieve long lasting and harder erections. Since citrulline is a precursor for arginine and arginine is a precursor to nitric oxide, you can combine the two for enhanced sexual pleasure and vascular health.
But you’re probably not eating six cups of watermelon every day, and actually it isn’t recommended. Watermelon is high in fructose (fruit sugar) and it’s a natural diuretic, so you’d be spending a whole lot of time in the bathroom.
In addition to watermelon, citrulline is found in cucumbers and cantaloupe, at very low levels, as well as the milk protein casein. But since it is a nonessential amino acid, you don’t have to rely on getting citrulline from food. It is manufactured from other nutrients in your body, however, you only manufacture it if you are young and healthy and producing those other essential nutrients in adequate amounts!
The citrulline and arginine combination plays an essential role in your body
Citrulline, like arginine, is important in vasodilation, the widening of blood vessels, resulting from relaxation of smooth muscle cells within the vessel walls, especially in the large arteries and veins and smaller arterioles.
The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax. This results in a relaxing of the blood vessels, and increased blood flow.
In the body, citrulline is converted to the amino acid arginine, which goes on to make another important substance—nitric oxide. When citrulline enters the kidney, vascular endothelium and other tissues, it can be readily converted to arginine, thus raising plasma and tissue levels of arginine and enhancing nitric oxide production.2
The importance of nitric oxide to healthy blood flow
As stated, nitric oxide is integral to relaxing blood vessels which is necessary for healthy blood flow to the heart and genital area in both men and women, and throughout the body. Nitric oxide helps the blood vessels maintain their flexibility so that the blood flow is unrestricted. This, in turn, helps maintain healthy blood pressure, and a healthy sexual response.
When your vascular system is working efficiently there is less chance that a blood clot will form, which means there is less chance of having a heart attack or stroke.
Nitric oxide helps prevent blood clots because it prevents blood aggregation or platelets from becoming sticky. When platelets are not sticky they can move in a single file through the capillaries.
But if they are sticking together it’s like trying to move a dozen people through a crack in the wall. There is nowhere for the platelets to go, so a blood clot forms.
Additionally, nitric oxide works as an antioxidant that reduces the possibility of immune cells adhering to artery walls. This helps keep down inflammation,
which most health professionals agree is a major cause of the plaque formation that contributes to atherosclerosis.
What inhibits adequate nitric oxide production?
– People who have atherosclerosis, diabetes or hypertension (high bloodpressure) often show impaired nitric oxide pathways.3
– Over-consumption of salt can impair nitric oxide production.4
– Aging—as we get older there is a decrease in nitric oxide production because the body makes less citrulline and arginine.5
Boosting nitric oxide production with nutritional supplements
Supplemental arginine helps the body produce more nitric oxide, and it helps with conditions that improve when blood vessels are relaxed, such as atherosclerosis and intermittent claudication (difficulty walking due to pain in leg muscles because of inadequate blood supply).
Even more importantly, new studies are showing that supplemental citrulline also assists in nitric oxide production by boosting blood levels of arginine. It does this because it is more readily absorbed and bioavailable than arginine alone, and it bypasses metabolism in the liver and gastrointestinal tract and is readily absorbed in the kidneys.6, 7
Citrulline and arginine scientific studies
In the first study to show that oral supplementation with citrulline raises blood levels of arginine, 20 healthy volunteers were given 6 different dosing regimens of placebo, citrulline, and arginine.
After one week of oral supplementation, the citrulline dose increased plasma arginine concentration more effectively than arginine alone.8
A study in humans also showed the citrulline supplementation’s “time release” effect on arginine production. In this study an oral dose of 3.8 grams of citrulline resulted in a 227% peak increase in plasma arginine levels after 4 hours, compared with a 90% peak increase with the same dose of arginine.7,9
Thus, acute oral administration of citrulline appears to be considerably more efficient at raising plasma levels of arginine over the long term than arginine itself.7
Reduces blood pressure
In another recent study, citrulline supplementation was shown to reduce blood pressure in 17 young (average age 21.6 years) men with normal blood pressure after they were submitted to a cold pressor test (CPT). (A cold pressor test is a cardiovascular test done by having the subject immerse his hand into a bucket of ice water for one minute. Blood pressure and heart rate are then evaluated.)
Even more importantly, new studies are showing that supplemental citrulline also assists in nitric oxide production by boosting blood levels of arginine.
The men were randomly assigned to four weeks of oral citrulline (6 grams/day) or placebo in a crossover design. Blood pressure was measured after the blood pressor test. The results showed that compared to placebo, oral citrulline decreased brachial systolic blood pressure (-6 +/- 11 mm Hg), aortic systolic blood pressure (-4 +/- 10 mm Hg), and aortic pulse pressure (-3 +/- 6 mm Hg) during CPT but not at rest, suggesting improved production of nitric oxide under stress.10
Boosts immune system function
Citrulline’s beneficial effects on nitric oxide were also demonstrated in a group of male professional cyclists who took 6 grams of oral citrulline before a race. Researchers found that the racers’ levels of arginine increased, as well as their neutrophil immune cells.11
Citrulline’s enhancement of immunity may benefit endurance athletes as it has long been noted that immune defenses drop after an intense athletic event, increasing susceptibility to infection.12
Pharmaceutical drugs that stimulate nitric oxide production
Of course “Big Pharma” has developed a number of drugs that work to increase the production of nitric oxide in the body, but as usual they don’t work with the body like natural amino acids do and they are loaded with side effects.
Nitroglycerin and amyl nitrite serve as vasodilators because they are converted to nitric oxide in the body.
Sildenafil citrate, popularly known as Viagra®, stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis.
But as mentioned, these drugs come with a long list of side effects, including headache, vision impairment, flushing, and rare but serious effects including heart attack and stroke.
Taking supplemental citrulline in combination with arginine is a great way to relax your blood vessels and avoid plaque build-up without drug side effects.
What to look for in a supplement
For each gram consumed, citrulline is more effective at raising nitric oxide levels (in vascular endothelium) than arginine alone. This is because approximately 50% of the arginine gets converted into other amino acids by the intestines and the liver. As the conversion of citrulline to arginine is not immediate, arginine will provide faster results.
As a convenient daily supplement in capsule form, citrulline is the best choice. This is because 6 grams (6,000 miligrams) of arginine is required to gain benefits. For those wanting to avoid swallowing a hand full of capsules, look for an arginine drink mix. Avoid pure arginine powder as the taste is awful, and the pH can burn the throat.
Taken together, you can get an immediate boost of nitric oxide production from the arginine, while allowing the citrulline time to produce additional arginine, for prolonged nitric oxide production.
This one-two punch of arginine and citrulline is a promising treatment for cardiovascular disease involving arginine deficiencies, reduced nitric oxide availability, and vascular dysfunction.
Together, citrulline and arginine supplementation is a natural and safe means of providing your body arginine, both short and long term. This combination can increase the natural production of nitric oxide, help reduce your chances of having a heart attack or stroke, boost your immune system, and improve your love live, all without the side effects of pharmaceutical drugs.
How are citrulline and arginine related?
As soon as citrulline enters the kidney, vascular endothelium and other tissues, it is converted into arginine. Plasma and tissue levels of arginine increase, which is necessary for the production of nitric oxide and relaxation of blood vessels.
An additional benefit of supplemental citrulline is that it helps eliminate ammonia, a highly toxic substance, from the liver.
Will citrulline and arginine help my sex life?
The answer is yes. Arginine has been well studied for its ability to enhance sexual satisfaction. Both men and women report longer and more intense orgasms when their intake of arginine increases. Additionally, arginine is often used by men to achieve long lasting and harder erections.
Since citrulline is a precursor for arginine and arginine is a precursor to nitric oxide, you can combine the two for enhanced sexual pleasure and vascular health.
Collins JK, Wu G, Perkins-Veazie P, Spears K, Claypool PL, Baker RA, Clevidence BA. Nutrition. 2007 March.
Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):275-90.
Dessy, C.; Ferron, O. (2004). “Pathophysiological Roles of Nitric Oxide: In the Heart and the Coronary Vasculature”. Current Medical Chemistry – Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 3 (3): 207–216.
Osanai, T; Fujiwara, N; Saitoh, M; Sasaki, S; Tomita, H; Nakamura, M; Osawa, H; Yamabe, H et al. (2002). “Relationship between salt intake, nitric oxide and asymmetric dimethylarginine and its relevance to patients with end-stage renal disease.”. Blood purification 20 (5): 466–8. doi:10.1159/000063555. PMID 12207094
Kang L, Reyes RA, Delp, JM. Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2. Am J Physiol Heart Circ Physiol. 2009 September; 297(3): H1087–H1095. Published online 2009 July 17. doi:
Cynober L. Pharmacokinetics of arginine and related amino acids. J Nutr. 2007 Jun;137(6 Suppl 2):1646S-1649S.
Romero M, Platt D, Caldwell R, Caldwell R. Therapeutic Use of Citrulline in Cardiovascular Disease. Cardiovascular Drug Reviews Vol. 24, No. 3–4, pp. 275–290.
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Boger RH. Pharmacokinetic and pharmacodynamic properties of oral Citrulline and Arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008 Jan;65(1):51-9. Epub 2007 Jul 27.
Kuhn KP, Harris PA, Cunningham GR, Robbins IM, Summar ML, Christman BW. Oral citrulline effectively elevates plasma arginine levels for 24 h in normal volunteers. Circulation AHA Scientific Sessions 2006; abstract 1692, p. II-1339.
Figueroa A, Trivino JA, Sanchez-Gonzalez MA, Vicil F. Oral Citrulline supplementation attenuates blood pressure response to cold pressor test in young men. Am J Hypertens. 2010 Jan;23(1):12-6. Epub 2009 Oct 22.
Sureda A, Cordova A, Ferrer MD, Tauler P, Perez G, Tur JA, Pons A. Effects of Citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. 2009 Sep;43(9):828-35. Epub 2009 Jul 6.
Chinda D, Nakaji S, Umeda T, Shimoyama T, Kurakake S, Okamura N, Kumae T, Sugawara K. A competitive marathon race decreases neutrophil functions in athletes.Luminescence. 2003 Nov-Dec;18(6):324-9.
Halstead, Bruce W., M.D. The Science of EDTA Chelation Therapy. Golden Quill Publishers, Inc., Colton, CA., 1979.
Robbins, S.L.; Cotran, R.S.: and Kumar, V., eds. Pathological Basis of Disease. New York: W.B. Saunders, 1984.