Creatine Hydrochloride as “GRAS” 2017-12-09T15:42:48-04:00


(Generally Recognized as Safe)

By Prevailing Opinion of the Scientific Community


Creatine supplements are commonly used as athletic aids to increase high-intensity athletic performance. Though researchers have known of the use of creatine as an energy source by skeletal muscles since the beginning of the 20th century, augmenting endogenous creatine with creatine supplements was popularized for performance-enhancement in the early 1990’s.

In 1912, Harvard University researchers found proof that ingesting creatine can safely and dramatically boost the creatine content of the muscle.1 In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.

At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993.

There are a number of forms of creatine, but the most common is creatine monohydrate whereby creatine is conjugated with a molecule of water (CM). CM is a basic “salt” of creatine. A number of methods for ingestion of Creatine exist. For example, CM in it’s crystalline form as a powder mixed into a drink, as a capsule, or caplet / tablet, or even from dietary sources such as red meat. Creatine salt supplements become the free form of creatine when ingested and taken up by the body.

Creatine hydrochloride (C-HCl) is also a salt of creatine. It is the same category of compounds as the other salts of creatine, like CM. The creatine salt category is considered GRAS by the scientific community. CM is considered GRAS by the scientific community and with regard to C-HCl, it’s salt form is more symbiotic to the human body (and specifically the G.I. tract) than other creatine salts because of it’s conjugation with an HCl molecule which is consistent with the contents of the stomach’s digestive juices (hydrochloric acid). C-HCl breaks down into the two simple molecules of creatine and hydrochloric acid, both GRAS and both endogenous to the human body.

A study on the characteristics of C-HCl and other salts demonstrates that it behaves in the blood compartment in an equivalent manner to creatine monohydrate and other GRAS creatine salts. 12


Studies indicate that supplementation with creatine salts in healthy individuals is safe, although those with renal disease may avoid it due to possible additional stress on renal function. 2, 3, 4, 5 Longer-term studies have been done and also demonstrate safety. 6, 7, 8 There have been reports of muscle cramping when creatine users do not maintain adequate hydration but a study showed no reports of muscle cramping in subjects taking creatine salt supplements during various exercise training conditions in trained and untrained endurance athletes. 9, 10

Other experiments have shown that supplementation with creatine salts improved the health and lifespan of mice. 11 Whether these beneficial effects would also apply to humans is uncertain and not claimed herein.

Additionally, safety and toxicity studies have were performed on a related creatine supplement where C-HCl was a minor, non-targeted compound in the formulation. Various dosages included an upper range (super-therapeutic) of supplement was given to Sprague-Dawley rats where doses of C-HCl could be calculated at a human equivalent of approximately 600mg (within normal range of recommended C-HCl dosing). Subsequent subject-animal assessment, blood chemistry profiles, and necropsy analysis of organ conditions, showed no adverse effects, organ lesions, or other toxicity indications. These results were submitted to the FDA as a part of an approval and allowance process for a New Dietary Ingredient. 13

Over the past 6 years, millions of doses of C-HCl have been consumed with no adverse effects and no reported health issues. Experts in pharmacology, toxicology, and pathology have affirmed the safe status of C-HCl.

In summary, like other creatine salts, creatine hydrochloride is part of a category of compounds that is generally recognized as safe (GRAS) by the scientific community; and both data and consumer experience substantiate such a classification.


1) Folin O, Denis W (1912). “Protein metabolism from the standpoint of blood and tissue analysis. Third paper, Further absorption experiments with especial reference to the behavior of creatine and creatinine and to the formation of urea.”. Journal of Biological Chemistry 12 (1): 141–61.

2) Graham AS, Hatton RC (1999). “Creatine: a review of efficacy and safety”. J Am Pharm Assoc (Wash) 39 (6): 803–10; quiz 875–7. PMID 10609446.

3) Creatine’s Side Effects. Fact or Fiction?, An interview of Professor Jacques R. Poortmans

4) Poortmans J. R., Francaux, M. (September 2000). “Adverse effects of creatine supplementation. Fact or Fiction?”. Sports Medicine 30: 155. doi:10.2165/00007256-200030030-00002. PMID 10999421.

5) Robinson, T.M.; Sewell, D.A., Casey, A., Steenge, G. & Greenhaff, P.L. (2000). “Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function”. British Journal of Sports Medicine 34 (4): 284–288. doi:10.1136/bjsm.34.4.284. Retrieved 2007-04-12.

6) Mayhew DL, Mayhew JL, Ware JS (2002). “Effects of long-term creatine supplementation on liver and kidney functions in American college football players.”. Int J Sport Nutr Exerc Metab. 12 (4): 453–60. PMID 12500988.

7) Poortmans, J.R.; Francaux, M. (1999-08-01). “Long-term oral creatine supplementation does not impair renal function in healthy athletes”. Medicine & Science in Sports & Exercise (Lippincott Williams & Wilkins, Inc.) 31 (8): 1108–1110.
doi:10.1097/00005768-199908000-00005.;jsessionid=Gp1DhynbQLLsXbhQ5jPbyL6YGqpGx9WhpkWBwbJJX1Wnv15v6CRp!-890758831!-949856145!8091!-1. Retrieved 2007-04-12.

8) Kreider, R.B.; Melton, C., Rasmussen, C.J., Greenwood, M., Lancaster, S., Cantler, E.C., Milnor, P. & Almada, A.L. (2004-11-01). “Long-term creatine supplementation does not significantly affect clinical markers of health in athletes”. Molecular and Cellular Biochemistry (Springer Netherlands) 244 (1-2): 95–104. doi:10.1023. Retrieved 2007-04-12.

9) Kreider R. (1998). “Creatine: The Ergogenic/Anabolic Supplement”. Mesomorphosis 1 (4). Retrieved 2007-04-12.

10) Kreider R, Rasmussen C, Ransom J, Almada AL. (1998). “Effects of creatine supplementation during training on the incidence of muscle cramping, injuries and GI distress.”. Journal of Strength Conditioning Research 12 (275).

11) Bender A, Beckers J, Schneider I, et al. (September 2008). “Creatine improves health and survival of mice”. Neurobiol. Aging 29 (9): 1404–11. doi:10.1016/j.neurobiolaging.2007.03.001. PMID 17416441.

12) Gufford, B, et al. “Physiochemical Characteristics of Creatine N-Methylguanidium Salts”. Journal of Dietary Suppl., Informa Healthcare, 2010.

13) FDA submission of new creatine safety and toxicity results from the University of Missouri Medical Center, Dept. of Veterinary Research, 2004.

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