The Discovery of Creatine: From Mystery to Modern Supplement

Even though the salubrious nature of meat was well understood for centuries, at least from observation, the mechanisms behind its health-giving properties went completely unrecognized, undefined, and unnoticed until the middle portion of the 19th century. That’s when the crystalline form of creatine was first discovered in the muscle tissue of meat.

The discovery of creatine in 1832 by French chemist Michel Eugène Chevreul was one thing, but researchers were still well short of understanding anything about how creatine functioned, or even what it was. For context, creatine was identified several decades before concepts like calories were unearthed, and approximately one decade before protein was fully comprehended as a macronutrient that helped to build and repair muscle tissue. 

Because of the unique era in which creatine was discovered, how often the science of biological science was forced to adjust to new information, and also how challenging it was for the experts of the era to accurately categorize all of the information, the discovery of creatine and the recognition of its benefits were events that were far removed from one another.

Creatine is a Mysterious Substance

Well over a decade after creatine’s discovery, The Manchester Courier published an article stating how creatine, “discovered by M. Chevreul of Paris, appeared to perform some functions in the animal body, but we did not know what.” In addition creatine was incorrectly understood to exist in its greatest abundance in chickens rather than in beef, evidenced by the statement that creatine was present in “fowl” at a ratio of “about three parts out of every 1,000, while 1,000 parts of beef contained only a fraction of a part.”

Moreover, the conversation surrounding nutrition was fraught with misinformation and pseudoscience, and the failure to quantify creatine was minimal in comparison to the struggle to define it.

Creatine is Politicized

Just because a chemical compound was present in muscle, that didn’t automatically mean its presence was productive. As such, one of the common deductions about creatine — especially because it initially couldn’t be differentiated from its waste byproduct creatinine — is that creatine was a waste product in its own right. As such, this led to willful misunderstandings about how people should respond to the knowledge of its presence.

For instance, in an open debate about the proper way to apprehend the presence of creatine in meat, and 1856 edition of The Hull Packet and East Riding Times of England rejected the proposal of a scientist by the name of Liebig that creatine might have contributed to “a large part in the vital actions” of vertebrate animals. 

“We think Robin, and Kerdell, and Lehmann have satisfactorily shown creatine to be not an organic principle, but the product of disintegration; and even should we accept it as an organic principle, we must demur against the leap in logic which jumps to the conclusion of its playing a great part in the vital actions,” noted the publication.

The reason for the objection was rooted in a prevailing argument of the time that horse meat was not suitable for consumption, resulting in a seeming prejudice in favor of creatine being an unhealthy waste product so that its presence could be used to support the prohibition against consuming horse flesh.

To be clear, creatine serves as a form of stored energy while creatinine is the waste product that forms after creatine breaks down after it is used. This inability to differentiate between the two crystalline products — one representing the potential form of energy and the other representing expended energy — resulted in several misguided conclusions being drawn about what creatine’s role was within human anatomy.

On the other end of the spectrum, the presumed healthful essence of creatine was cited during a meeting of one of England’s vegetarian societies in 1853. Following the same pattern of misunderstanding — often willfully — the flow of nutrients through food, the society argued that no nutrients could possibly be present in animal sources that the animal had not first acquired from one or more plant sources.

“If we slaughtered an ox or a sheep, and took a portion of its body into our own body, we could only derive from it the same elements of food which were in the vegetables on which that animal had been fed, except that there was on peculiar element, called creatine, to be obtained from the flesh, but even that could be obtained from other sources,” noted the presiding society member, Mr. Simpson.

The point by Mr. Simpson betrays a common misconception about the different physiological processes at work within different species of animals — including mammalian species — and how consuming identical forms of food could yield different physiological outcomes in each species. One of the most common comparisons is between humans and gorillas, with vegetarians often noting that gorillas are able to craft immense muscle mass with a vegetarian diet, with the implication being that humans should be able to do the same.

These comparisons ignore the innate differences between humans and gorillas. Gorillas have thicker bones than humans, coupled with a valuable mixture of high levels of testosterone and insulin-like growth-factor 1 (IGF 1), and very low levels of myostatin, which is a protein that works to inhibit muscle growth. Beyond this, they also have gut bacteria that makes it easier to extract amino acids from plant fibers for muscle growth and repair. 

In short, adaptations like these enable certain animal species to extract value from foods that might seem attractive to humans, but which humans are incapable of attaining.

Consequently, an adherence to vegetarianism and veganism has often resulted in lower average levels of creatine in these groups, which went unrealized for centuries. Studies would later demonstrate how supplementation with creatine rapidly increases the creatine levels of vegetarians and vegans, with these groups often achieving the most measurable rapid benefits from creatine supplementation. 

In fact, a systematic review of nine studies evaluating creatine supplementation in vegetarians showed that the group not only had lower baseline levels than their omnivorous peers, but their bodies were so responsive to creatine after being deprived of it for so long that they seemed to engage in “super compensation” by rapidly inflating their creatine quantities to average levels higher than those of omnivores who also received creatine supplements. [1]

Creatine Catches On

The general assumption that creatine was a valuable nutrient carried forth into the later decades of the 19th century, but its precise role remained undefined. Still, the growing popularity of meat extracts as a “restorative” consumer product, and the fact that creatine was one of the nutrient components of meat that retained a strong presence in the meat’s extract, led many observers to presume that creatine was the nutrient that gave meat extract whatever value it possessed.

It was during this era, in the late 1860s, that the value of an isolated creatine supplement was first proposed.

“Should it be found that a solution of pure creatine has the same stimulating effect of a cup of beef-tea made from Liebig’s extract, it will probably be to this source that we must look for our supply; and if to this solution be added a due proportion of phosphate of potash and common salt, we should have a more agreeable drink than we now possess in the solution of the extract, and we should know, what at present we do not, what we are swallowing,” wrote The Manchester Weekly Times.

Even so, as the 19th century wore on, creatine continued to suffer from its misidentification as a waste product despite all evidence to the contrary. In an article from Dr. Alfred W. Perry published in December 1880, it was revealed how therapeutic science of the era hinted that animals that were fed beef extract “die more quickly than animals deprived of all food,” that “creatine and potass[ium] salts seem to paralyze the heart,” and that creatine and creatinine, owing to the fact that they were excreted substances found in urine, “could hardly be supposed to be suitable nutriment.”

“They give to beef tea or extract that pungent taste irritation to the (mouth) — the potassium salts cause the purging which everyone must have noticed after giving beef tea,” insisted Perry.

Creatine is Misclassified

Even though the properties of creatine had rightly been identified as “restorative,” the failure to accurately categorize and separate both the positive effects of food and the chemical compounds that contributed to those positive feelings led to some comparisons that are quite misguided when viewed through a retroactive lens.

In response to the question, “What is creatine?” The Hull Packet correctly identified it as a “soluble crystalisable compound” that  provided meat extracts with their value. From there, the publication made several grave mischaracterizations with respect to creatine’s contemporaries on the nutrient chart.

“In the first place, creatine is a stimulant, just as much as alcohol, or theine, or caffeine, or theobromine are, the three latter being crystalisable bodies found in tea, coffee, and cocoa respectively,” continued The Packet. “Creatine, however, leaves no reaction on the human organism; all the others do.”

The notion that creatine — the foremost contributor to the body’s natural stores of adenosine triphosphate — was once hypothesized to be equivalent to what are now respectively the most popular commercial depressant and stimulant in the world, now seems patently absurd. However, this means of categorization becomes more understandable when considering how loosely the term “stimulant” was defined during the era.

Contemporarily, we have overwhelmingly more scientific insight into how differently stimulants all operate even within the same category. Technically, a stimulant is a drug that increases alertness, and its definition immediately disqualifies creatine from inclusion because it is not a drug. Then, within the broader category of stimulants, some stimulants operate by directly increasing the activity of neurotransmitters like dopamine, while others inhibit the ability of receptors to perceive feelings of sleepiness or fatigue.

Caffeine falls into the latter category of stimulants; it temporarily prevents the adenosine receptors of your brain from registering fatigue. This predictable capability of caffeine would see it refined into a nutritional supplement. The International Society of Sports Nutrition position regarding caffeine is that it can improve “muscular endurance, movement velocity and muscular strength, sprinting, jumping, and throwing performance, as well as a wide range of aerobic and anaerobic sport-specific actions.” [2]

Creatine delivers energy to users in very different ways than caffeine, and in a fashion that is arguably both more subtle and healthy. The reason for this is creatine boosts natural reserves of adenosine triphosphate, which is your body’s preferred form of fuel for biological processes requiring immediate energy. While caffeine triggers alertness by conditioning your brain and body to resist natural impulses to rest, creatine provides your brain with a reserve of natural energy to tap into. To put it simply, while caffeine helps your body to ignore its shortage of energy, creatine actually reinforces your body’s energy supply.

In recognition of this feature, the ISSN position on creatine states “there is no scientific evidence that the short- or long-term use of creatine monohydrate has any detrimental effects on otherwise healthy individuals.” [3] This is in contrast with caffeine, which comes with an ISSN warning that “adverse effects on sleep or feelings of anxiety following caffeine ingestion may be attributed to genetic variation associated with caffeine metabolism, and physical and psychological response.”  [2]

The belief in alcohol’s stimulating properties is a result of a common initial response to intoxication, which is an increase in dopamine, which can cause a sudden spike in pleasant feelings, which is often perceived as an uptick in energy. However, alcohol is officially a central nervous system depressant that slows down brain processes, and therefore hinders the optimal functioning of both mind and body.

In comparison to both creatine and caffeine, alcohol has long been dismissed as a net negative in the pursuit of all forms of athletic accomplishment. The American College of Sports Medicine’s 1982 position statement on alcohol concluded that alcohol consumption was associated with “decreased psychomotor coordination, decreased maximal oxygen consumption, and impaired temperature regulation,” while subsequent studies identified how alcohol both caused dehydration, and worsened the effects of existing dehydration. [4]

On the Precipice of Recognition 

The discovery of creatine failed to set the world of nutrition on fire, as it occurred during an era when comprehension of nutrition science was uniquely challenging, and when speculation about creatine’s physiological role was fraught with political pressures. 

Despite these obstacles, there was enough anecdotal evidence present that several of the era’s specialists were able to correctly guess that creatine’s presence in food was a net positive to physical productivity, and the scientific breakthroughs of the 20th century would concretize these theories, directly leading to the first attempts to isolate creatine and develop it into a supplement.

Sources

1. Kaviani M, Shaw K, Chilibeck PD. Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review. Int J Environ Res Public Health. 2020 Apr 27;17(9):3041. doi: 10.3390/ijerph17093041. PMID: 32349356; PMCID: PMC7246861.

2. Guest NS, VanDusseldorp TA, Nelson MT, Grgic J, Schoenfeld BJ, Jenkins NDM, Arent SM, Antonio J, Stout JR, Trexler ET, Smith-Ryan AE, Goldstein ER, Kalman DS, Campbell BI. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021 Jan 2;18(1):1. doi: 10.1186/s12970-020-00383-4. PMID: 33388079; PMCID: PMC7777221.

3. Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2007 Aug 30;4:6. doi: 10.1186/1550-2783-4-6. PMID: 17908288; PMCID: PMC2048496.

4. Weaver CC, Martens MP, Cadigan JM, Takamatsu SK, Treloar HR, Pedersen ER. Sport-related achievement motivation and alcohol outcomes: an athlete-specific risk factor among intercollegiate athletes. Addict Behav. 2013 Dec;38(12):2930-6. doi: 10.1016/j.addbeh.2013.08.021. Epub 2013 Aug 29. PMID: 24064192; PMCID: PMC4249648.