Matthew Harmon, USJ Dietetic Intern, ’17
About a month ago, a supplement rep came to my school to talk about the company’s catalog of products, and given my long history of working with supplements, I was very excited about the lecture. The rep explained to the class about all of their various wonderful products, such as nutrition formulas for pediatrics that contain real food ingredients, specialized tube feeding formulas and many others. As the rep was explaining about this next supplement, my ears immediately perked up because this product continues to use L-arginine as an active ingredient in their wound healing supplement. Most researchers in the sports nutrition world have already taken their attention off of L-arginine and redirected their work onto L-citrulline. Athletes, both the runner and the weight lifter, now recognize its benefits in decreasing fatigue and enhance endurance. So, it begs the following question: If sports nutrition supplement companies are making the switch, is it warranted for medical nutrition supplement companies to follow?
L-Arginine and Wound Healing
Here is a quick overview of L-arginine: It is a conditional amino acid, manufactured endogenously in the body, and it can be consumed from various foods, turkey has the highest amount. The main benefits include the stimulation and release of growth hormones and insulin. But it really made its mark in the health world for its nitric oxide (NO) producing ability. Studies have demonstrated that NO is a key player in many biological processes, such as vasodilation, brain health and the immune system.
NO is a vasodilator. Vasodilation is a critical step in the recovery/wound healing process. NO participates in antimicrobial activities and allows for more blood flow into tissues and organs, which allows the inflamed/injured site to receive an increasing demand of nutrients and oxygen for optimal repair (1). In addition, ornithine plasma is increased, and it serves as an active player in collagen development and increases the wound integrity from breaking (2).
It is manufactured in the body and can be obtained from some fruits and vegetables, watermelon being the highest source. Like L-arginine, L-citrulline possesses the same ability to assist in the stimulation of growth hormones, insulin and NO. This is accomplished by the kidneys by converting L-citrulline into arginine. In other words, health benefits are similar in a lot of ways due to the fact that it is a precursor to the amino acid, L-arginine.
L-Arginine versus L-Citrulline
Oral consumption of L-arginine poses several problems: The primary concern lies within absorption. Research has indicated its bioavailability ranges of 57–77% at a 6-gram dose, and 20% at 10 grams (3,4). Moreover, in the same study conducted by Tangphao O, et al., noted a range as low as 5–50% absorption (4). The other possible concern, if taken with food, the absorption of the amino acid can decrease, making it cumbersome for consumers/patients that may follow a random eating schedule. Therefore, in order to maximize L-arginine absorption, it is best recommended that the amino acid should be taken on an empty stomach. Furthermore, large doses of L-arginine have been reported to cause gastrointestinal distress and diarrhea.
For athletes, it seems that the research suggests the effective dosage is 6 grams of L-citrulline, and compounded to a malate molecule. It does not trigger gastric distress or diarrhea when taken at 15grams (5). It is absorbed at a higher amount in the gut than L-arginine (6). Studies suggest that approximately 83% of the supplement is absorbed by the kidneys (7). Moreover, L-citrulline consumed at 0.18g/kg produces an increase and a sustainable plasma level of arginine than arginine itself (8). It also produces a higher plasma count of ornithine by approximately 200 percent (9), which has been demonstrated in studies as one of the key amino acids involved in the healing process (2).
Although the athlete’s motivation is a lot different than the patient, both consumers can still receive L-citrulline’s benefits. As stated earlier, it does not cause any issues with intestinal distress. It is better absorbed and outputs a higher arginine and ornithine serum count in the body over L-arginine supplementation itself. Therefore, in theory, a higher increase of arginine and ornithine in the human body should result in a better wound healing supplement. So, back to my question: if sports nutrition supplement companies are making the switch, is it warranted for medical nutrition supplement companies to follow?
I think the answer is yes.
- Stechmiller JK, Childress B, Cowan L. Arginine Supplementation and wound healing. Nutr Clin Pract. 2005;20(1):52–61. doi:10.1177/011542650502000152. http://ncp.sagepub.com/content/20/1/52.long. Accessed October 21, 2016.
- Shi HP, Fishel RS, Efron DT, Williams JZ, Fishel MH, Barbul A. Effect of supplemental Ornithine on wound healing ☆☆☆. Journal of Surgical Research. 2002;106(2):299–302. doi:10.1006/jsre.2002.6471. http://www.sciencedirect.com/science/article/pii/S0022480402964711. Accessed October 21, 2016.
- Bode-Böger SM, Böger RH, Galland A, Tsikas D, Frölich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic–pharmacodynamic relationship. British Journal of Clinical Pharmacology. 1998;46(5):489-497. doi:10.1046/j.1365-2125.1998.00803.x. Accessed October 21, 2016.
- Tangphao O, Grossmann M, Chalon S, Hoffman BB, Blaschke TF. Pharmacokinetics of intravenous and oral l-arginine in normal volunteers. 1999;47(3). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014227/. Accessed October 21, 2016.
- Moinard C, Descartes UP, Nicolis I, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: The Citrudose pharmacokinetic study | British journal of nutrition | Cambridge core. British Journal of Nutrition. 2008;99(4):855–862. doi:10.1017/S0007114507841110. https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/dose-ranging-effects-of-citrulline-administration-on-plasma-amino-acids-and-hormonal-patterns-in-healthy-subjects-the-citrudose-pharmacokinetic-study/914C4C4EA85887DC2935740ACF8E36DE. Accessed October 21, 2016.
- Curis E, Crenn P, Cynober L. Citrulline and the gut: Current opinion in clinical nutrition & metabolic care. September 2007. doi:10.1097/MCO.0b013e32829fb38d. http://journals.lww.com/co-clinicalnutrition/pages/articleviewer.aspx?year=2007&issue=09000&article=00010&type=abstract. Accessed October 21, 2016.
- Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Article. 1981;241(6):473–480. http://ajpendo.physiology.org/content/241/6/E473.abstract. Accessed October 21, 2016.
- Rougé C, Robert CD, Robins A, et al. Manipulation of citrulline availability in humans. MUCOSAL BIOLOGY. 2007;293(5):1061–1067. doi:10.1152/ajpgi.00289.2007. http://ajpgi.physiology.org/content/293/5/G1061.long. Accessed October 21, 2016.
- Demura S, Yamada T, Yamaji S, Komatsu M, Morishita K. European journal of clinical nutrition – abstract of article: The effect of L-ornithine hydrochloride ingestion on performance during incremental exhaustive ergometer bicycle exercise and ammonia metabolism during and after exercise. European Journal of Clinical Nutrition. 2010;64(10):1166–1171. doi:10.1038/ejcn.2010.149. http://www.nature.com/ejcn/journal/v64/n10/pdf/ejcn2010149a.pdf. Accessed October 21, 2016.