L arginine or l citrulline for ed*

Arginine and Citrulline: A Review of Their Safety and Efficacy for Erectile Dysfunction & Beyond

Arginine and Citrulline: A Review of Their Safety and Efficacy for Erectile Dysfunction & Beyond

Jeremy Appleton, ND

Citrulline was first identified and isolated from the juice of the watermelon (Citrullus vulgaris) 3 This amino acid initially attracted little interest because it is a non-protein amino acid that was considered solely an intermediate metabolite in the formation of urea 4,5 However, newer research has accumulated because of its unusual metabolism 6 Citrulline is a non-essential amino acid, donor of arginine and NO, and (similar to glutamine) a conditionally-essential amino acid in intestinal pathology Its major pharmacological actions include: antioxidant; vasodilatory; decreasing leukocyte migration; restoring nitrogen balance and increasing muscle protein content as well as muscle protein synthesis; improving endothelial dysfunction; increasing argininosuccinate synthase expression in cancer cells; and preserving anti-inflammatory mediator response (in sepsis) 7


Citrulline acts as an arginine precursor in NO synthesis 13 and plays an important part in NO metabolism and regulation 14 Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver It may be a conditionally-essential amino acid in situations where intestinal function is compromisedIt is a precursor to the formation of LArginine and thus plays a vital role in Arginine recycling, which is an important factor in nitric oxide release. In fact, citrulline is thought to play a pivotal role in maintaining protein homeostasis, and should be considered in nutritional strategies for malnourished patients with compromised intestinal function 4

Clinical Uses of Arginine

Arginine in Erectile Dysfunction

Citrulline Indications

Citrulline in Erectile Dysfunction

In a single blind, short-term study of men with ED (erection hardness score of 3 out of 4), L-citrulline was given at dose of 15 g per day for a month It was concluded that citrulline was safe and psychologically well-accepted, and reported as very satisfying to the patients Although less effective than phosphodiesterase type-5 enzyme inhibitors, L-citrulline supplementation was associated with an improvement in erection hardness score, from 3 to 4 33

Significant adverse effects have not been observed with arginine supplementation; however, long-term studies are needed to confirm its apparent safety People with renal failure or hepatic disease may be unable to appropriately metabolize and excrete supplemental arginine and should be closely monitored when taking arginine supplements

It has been postulated, on the basis of older in vitro data 34 and anecdotal reporting, that arginine supplementation is contraindicated in persons with herpes infections (ie, cold sores, genital herpes) The assumption is that arginine might stimulate replication of the virus and/or provoke an outbreak; however, this caution has not been validated by controlled clinical trials

Bronchoconstriction is reportedly inhibited by the formation of NO in the airways of asthmatic patients, and a bronchoprotective effect of NO in asthma has been proposed 35 Specifically, airway obstruction in asthma might be associated with endogenous NO deficiency caused by limited availability of NO synthase substrate (ie, arginine)

Since polyamines act as growth factors for cancers, and arginine may stimulate polyamine synthesis, chronic administration of arginine in cancer patients should probably be avoided until information arises regarding the safety of this practice

Short-term administration of citrulline is safe and well tolerated No adverse effects were observed in healthy subjects that were given different loading doses of 2 g, 5 g, 10 g or 15 g 40 There is a dearth of reliable scientific data regarding its use in pregnancy and lactation

Jeremy Appleton, ND, has been a well-known writer and speaker on topics in natural medicine for nearly 20 years A graduate of Reed College and the National College of Natural Medicine (NCNM), Dr Appleton has been on the faculty at NCNM and Bastyr University He currently works as Director of Scientific Affairs for Nature’s Way brands (Nature’s Way, Enzymatic Therapy, Integrative Therapeutics, Boericke & Tafel, Wellesse) and lives in Portland, OR