L-arginine, N-acetyl-L-cysteine and coumarin show positive effects in reducing damage to blood vessels, A Randomized, Double-Blind, Placebo-Controlled Study

Author: Karin Schön, Christiane Jensch, Antonella Allegrini, Pietro Riva, Giovanna Morazzoni


This study aimed to investigate the effects of l-arginine, n-acetyl-l-cysteine and cumarine repairing damaged blood vessels in middle-aged Japanse adults. We conducted a randomized, double-blind, placebo-controlled study on 86 men and 42 women aged 35-65 years old with damaged blood vessels. The participants were randomized to receive tablets containing l-arginine (10 mg/day), n-acetyl-l-cysteine(7 mg/day) and cumarine(5 mg/day) or placebo, for 12 weeks. Complement component C4, brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured before and after 4, 8, and 12 weeks of treatment. After 12 weeks the Complement component C4 reached the optimum range from 16 – 47 mg/dl for 98% (n=63) of the parcipitant in the control group. However there were no significant changes in the placebo group. Consumption of l-arginine, n-acetyl-l-cysteine and cumarine could help maintain healthy blood vessels and normal C4 levels in this population.

Conflicts of Interest

The authors declare no conflict of interest.


1. Lillibridge C. B., Docter J. M., Eidelman S. Oral administration of n-acetyl cysteine in the prophylaxis of “meconium ileus equivalent. The Journal of Pediatrics. 1967;71(6):887–889. doi: 10.1016/s0022-3476(67)80019-2.
2. Gracey M., Burke V., Anderson C. M. Treatment of abdominal pain in cystic fibrosis by oral administration of n-acetyl cysteine. Archives of Disease in Childhood. 1969;44(235):404–405. doi: 10.1136/adc.44.235.404.
3. Vasdev S., Singal P., Gill V. The antihypertensive effect of cysteine. The International Journal of Angiology: Official Publication of the International College of Angiology, Inc. 2009;18(1):7–21. doi: 10.1055/s-0031-1278316.
4. Demirkol O., Adams C., Ercal N. Biologically important thiols in various vegetables and fruits. Journal of Agricultural and Food Chemistry. 2004;52(26):8151–8154. doi: 10.1021/jf040266f.
5. Kerksick C., Willoughby D. The antioxidant role of glutathione and N-Acetyl-Cysteine supplements and exercise-induced oxidative stress. Journal of the International Society of Sports Nutrition. 2005;2(2):p. 38. doi: 10.1186/1550-2783-2-2-38.
6. Fass D., Thorpe C. Chemistry and enzymology of disulfide cross-linking in proteins. Chemical Review. 2018;118(3):1169–1198. doi: 10.1021/acs.chemrev.7b00123.
7. De Flora S., Izzotti A., D’Agostini F., Balansky R. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis. 2001;22(7):999–1013. doi: 10.1093/carcin/22.7.999.
8. Halasi M., Wang M., Chavan T. S., Gaponenko V., Hay N., Gartel A. L. ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors. Biochemical Journal. 2013;454(2):201–208. doi: 10.1042/bj20130282.
9. Uraz S. N-acetylcysteine expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats. Scandinavian Journal of Clinical and Laboratory Investigation. 2013;73(1):61–66. doi: 10.3109/00365513.2012.734859.
10. Zhitkovich A. N-Acetylcysteine: Antioxidant, aldehyde scavenger, and more. Chemical Research in Toxicology. 2019;32(7):1318–1319. doi: 10.1021/acs.chemrestox.9b00152.
11. Livingstone C. R., Andrews M. A., Jenkins S. M., Marriott C. Model systems for the evaluation of mucolytic drugs: acetylcysteine and S-carboxymethylcysteine. Journal of Pharmacy and Pharmacology. 1990;42(2):73–78. doi: 10.1111/j.2042-7158.1990.tb05357.x.
12. Fries G. R., Kapczinski F. N-acetylcysteine as a mitochondrial enhancer: a new class of psychoactive drugs? Brazilian Journal of Psychiatry. 2011;33:321–322. doi: 10.1590/s1516-44462011000400003.
13. Jiao Y. N-acetyl cysteine depletes reactive oxygen species and prevents dental monomer-induced intrinsic mitochondrial apoptosis in vitro in human dental pulp cells. PLOS ONE. 2016;11(1) doi: 10.1371/journal.pone.0147858.e0147858
14. Rossignol D. A. The use of N-acetylcysteine as a chelator for metal toxicity. In: Frye R. E., Berk M., editors. The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine. Singapore: Springer Singapore; 2019. pp. 169–179.
15. Dean O., Giorlando F., Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011;36(2):78–86. doi: 10.1503/jpn.100057.
16. Tomàs Casanova M. G. N-Acetylcysteine: An old drug with variable anti-influenza properties. Journal of Controversies in Biomedical Research. 2016;2(1):1–8. doi: 10.15586/jcbmr.2016.13.
17. Redondo P., Jimenez E., Perez A., García-Foncillas J. N-acetylcysteine downregulates vascular endothelial growth factor production by human keratinocytes in vitro. Archives of Dermatological Research. 2000;292(12):621–628. doi: 10.1007/s004030000187.
18. Douiev L., Soiferman D., Alban C., Saada A. The effects of ascorbate, N-acetylcysteine, and resveratrol on fibroblasts from patients with mitochondrial disorders. Journal of Clinical Medicine. 2016;6(1) doi: 10.3390/jcm6010001.
19. Martina V. Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care. 2008;31(5):940–944. doi: 10.2337/dc07-2251.
20. Olsson B. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. European Journal of Clinical Pharmacology. 1988;34(1):77–82. doi: 10.1007/bf01061422.


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November 11, 2017