Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements

Abstract

Purpose

Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes’ workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups.

Conclusions

Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD_70/30 dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr–Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.

Keywords:

• Creatine
• l-arginine
• radioprotection

Acknowledgements

We thank Dr. Elina Arakelova (Institute of Molecular Biology NAS RA) for her valuable and helpful comments on the manuscript. We are also grateful to Mikayel Karapetyan for his technical help in the design of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data sharing is not applicable to this review article as no new data were created or analyzed in this study.

Additional information

Funding

This work has been supported by the Science Committee of the Ministry of Education, Science, Culture and Sports of the Republic of Armenia in the frames of the 20TTCG-1F003 and 21T-1F066 research projects.

Notes on contributors

Lyudmila Nersesova

Lyudmila Nersesova, PhD, is a Senior Scientist at the Laboratory of Experimental Biology of the Institute of Molecular Biology NAS RA, Yerevan, Armenia. Her main interest focuses on studying the role of creatine kinase as a biomarker of the impact ionizing and non-ionizing electromagnetic radiation as well as xenobiotics may cause to organism. Particularly under the spotlight comes the identification of new natural radioprotectors.

Mariam Petrosyan

Mariam Petrosyan, PhD, is a Junior Scientist at the Laboratory of Experimental Biology of the Institute of Molecular Biology NAS RA, Yerevan, Armenia. Her main interest is the identification and study of different radioprotective agents.

Gohar Tsakanova

Gohar Tsakanova, PhD, is the Deputy Director, a Leading Scientist and Head of the Laboratory of Experimental Biology at the Institute of Molecular Biology NAS RA, Yerevan, Armenia, as well as a Leading Scientist and Head of Laboratory of Experimental Biology at the CANDLE Synchrotron Research Institute. Her scientific interests include study of potential radioprotectors and radioenhancers, as well the studies of the biomedical effect of ultrashort pulsed electron beam irradiation.