Comprehensive Analysis of Creatine 

Creatine is an extremely well-studied subject. However, even through the hundreds of articles on the topic, not one covers the subject in every aspect a person might want. Not to mention, not enough people as the questions “how” and “why”. In this article, I will explain what creatine is, why it is important, how it interacts in our physiology, and all the most popular questions related to the subject – all backed with scientific literature. Let’s begin.
 

What is creatine?

Creatine is a nitrogenous organic compound. It is important to realize that creatine is a nitrogenous compound, because it shares this trait with protein molecules which are the only macronutrient with nitrogen attached to it. Why does that matter? Because the consumption of proteins allows the body to synthesize creatine endogenously (inside itself); the three ingredients needed to make creatine are the amino acids found in complete sources of protein (for example, meat). These three amino acids are glycine, arginine, and methionine [1][2].
 

Molecular creatine - notice the Nitrogen attached.

What does it do?

Our body’s metabolism is set up with two distinct metabolism pathways distinguished by the presence of oxygen. If oxygen is present, the body uses its aerobic metabolism (what we use the majority of the time). However, when we push our body hard, to a point where oxygen delivery is not fast enough, our body switches to an anaerobic metabolism. Why is this relevant to creatine?

It is relevant, because creatine is a major player in providing resources so that our anaerobic metabolism can function correctly. The anaerobic metabolism shifts seamlessly through the phosphocreatine system and anaerobic glycolysis, and for it to begin giving us energy, it needs creatine loaded into that phosphocreatine system. As this is not a metabolism article, I will not bog you down with details, but creatine is essential in the first 8-12 seconds of intense exercise (intensity defined by insufficient oxygen presence for a desired energy output) [3].

Creatine supplementation, from a performance stand point, can increase a person’s force production time during resistance training by about 8% [5][8].

There is also some research showing mechanistic data that creatine may have direct impact on protein synthesis via increased cell swelling causing proteins linked to the muscle cell membrane to activate downstream protein synthetic pathways [16]. Interestingly, creatine may also mitigate protein breakdown, so a doubling effect [17]. However, if the protein synthetic effect persists over weeks or months is unclear, in my eyes.


Other benefits of creatine?

While there have been a ton of studies conducted on creatine and creatine supplementation, there are few that have been conducted in areas other than ergogenic benefits. However, research is starting to shift that direction, and there is limited evidence appearing that creatine may have beneficial effect on ALS, multiple sclerosis, heart failure, Parkinson’s, among many other conditions [10]. Again, there is limited research on all this, so until further studies are conducted (especially longitudinal), just know that creatine supplementation has a definite impact on strength performance and certain creatine deficiency diseases.

Is it common to the body?

Yes, our body synthesizes creatine if the ingredients are given. This is yet another reason why consuming complete proteins is essential for our survival, because in this case, our body needs the three amino acids (glycine, arginine, and methionine) and an assortment of enzymes (not discussed here) to fulfill the demand for creatine. Of course, taking already synthesized creatine (referring to creatine supplementation) also has benefits to the phosphocreatine system by saturating the environment with a maximal amount of creatine – there are limitations to this, discussed later in “response".

Where is it synthesized?

As mentioned in the last section, creatine is essential to our optimal performance and that being the case; the body has the capacity to synthesize its own. It does this by synthesizing creatine in the liver, kidneys, and pancreas [4]. 95% of creatine is then stored and used in the muscles and makes up about 0.5% of the muscle weight [5]. The other 5% is stored in the kidneys, brain, liver, and testes [8].

How does it impact the muscle?

This has already been touched on, but creatine is ingested or synthesized and then is sent to the muscles. There, a creatine transporter allows creatine to saturate the myocyte (muscle cell) [6]. Then, the muscle is saturated with intracellular creatine, but for creatine to be of use, it needs to go through a further step. This step is done by phosphorylating creatine with the use of ATP to create intracellular phosphocreatine, and the more intracellular phosphocreatine, the more immediate energy is available for a few more seconds of performance [7].​

Explanation: Creatine goes to the muscles and saturates the cellular unit (myocyte/muscle fiber) to increase the available phosphocreatine levels inside the cell.

Is it safe?

Creatine has had many studies done to examine various aspects, and it is established that creatine is safe in acute (2 week) intake [9]. In terms of long term intake (months and years), there has been no evidence of serious complications. The worst, in healthy populations, is mild nausea from overconsumption and muscle cramping from use without proper hydration. In people with an unhealthy renal system (kidney damage of some sort), it is possible that excess creatine could put strain on the kidneys [10].

So, for healthy people, it is currently considered safe to supplement with creatine with normal dosage.


Does it impact my kidneys?

No. Kidney function is normally measured by creatinine clearance and no difference in clearance (which might indicate strain) is seen upon creatine supplementation [14].

Does it impact my blood pressure?

No. Blood pressure was shown to be relatively unaffected after several days and many weeks of creatine supplementation [14][15].
 

Dosage?

While some might recommend a “loading” phase for creatine, this is generally considered rather pointless – although, not harmful [5]. Typically, 2-5g a day is sufficient; aim closer to 5g if you are a larger individual as this will ensure muscle saturation.

Why 2-5g/day?

The body has a 2g/day turn over, and it synthesizes 1g/day endogenously, and another 1g/day comes in from diet to equate for that loss [8]. So, considering a person’s muscle mass, 2-5g/day would be sufficient to maximize creatine saturation of the myocytes (muscle cells).

Why not more?

The mentality of “more is better” is often a wrong one. In this case, human muscle has been estimated to hold a maximum of 150 mmol creatine/kg of muscle [5]. Oversaturation of the muscle would not make it inside the myocytes and would be excreted via the kidneys.

Timing of consumption?

There is not much data on this, but it is unlikely that timing, in terms of bioavailability, makes much of a difference. It might be advisable, according to the American College of Sports Medicine, to avoid consuming creatine pre-workout, as creatine could cause nausea and muscle cramping without proper hydration. Otherwise, it is likely perfectly alright to consume at one’s leisure.

Will I always gain weight if I supplement creatine?

Yes. Creatine is a molecule, a bit like sodium, that is followed by water. Where creatine goes, water follows. So, if you intake more creatine, water will also be drawn in. Total water weight gain will be somewhere between 1 – 3.5lbs (sometimes more) depending on the individual and amount of creatine used [12]. Luckily, water distribution is even across the body [11]. This water intake into the cells is due to a need to maintain intracellular concentration relative to the extracellular space.
 

Does everyone respond to creatine the same way?

Yes and no. Yes, creatine does not act differently in the body of one person to another – physiology is stable. However, some individuals do not respond to extra creatine intake [13]. Reasons for non-response are varied, but the top three reasons are [13]:

1. Lower amount of type II muscle fibers  - these muscle fibers are predominant in resistance exercises.
2. Higher innate intracellular levels of creatine – if the muscle is already maximally saturated, supplementation will have no effect.
3. Large amounts of Fat Free Mass (including muscle) – while I would consider this lower in likelihood, this could have an impact.

What type of creatine is best?

Creatine Monohydrate; It is effective, simple, and the cheapest. I would go into a comparison of all the different types, but that would take quite a bit of effort just to come to the same conclusion. All creatine will make one gain weight, without exception, so creatine monohydrate is the best bang for the buck.
 

SUMMARY

There we have it. All creatines do the same thing, all creatines retain water, and creatine does aid, those who respond to it, slightly. There is no need to take in more than 2-5g/day, and yes it is safe to consume if your kidneys are fully functioning; the most cost effective creatine is creatine monohydrate. Even if we do not supplement with creatine, our metabolism uses creatine, and as such, it is synthesized in the body, as well as gathered in our diet, so avoiding it is a futile attempt.

Writer: Nicolas Verhoeven
This is educational material only and not meant to be prescripton, consult your physician before making any changes.

References

[1] Brosnan, J. T., Da Silva, R. P., & Brosnan, M. E. (2011). The metabolic burden of creatine synthesis. Amino Acids, 40(5), 1325-1331. http://www.ncbi.nlm.nih.gov/pubmed/21387089

[2] Taegtmeyer, H., & Ingwall, J. S. (2013). Creatine--A Dispensable Metabolite? Circulation Research, 112(6), 878-880. http://circres.ahajournals.org/content/112/6/878.extract

[3] Phosphocreatine. (n.d.). Retrieved from http://www.udel.edu/chem/C465/senior/fall00/Performance1/phosphocreatine.htm.html

[4] Ehrlich, S. D. (2014, June 26). Creatine. Retrieved from https://umm.edu/health/medical/altmed/supplement/creatine

[5] Muscle Physiology - Creatine. (n.d.). Retrieved from http://muscle.ucsd.edu/musintro/creatine.shtml

[6] Christie, D. L. (2007). Functional insights into the creatine transporter. Subcell Biochemistry,46, 99-118. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18652074

[7] Quinnipiac University Chemistry in Sports and Fitness: A Case Study Collection - Creatine Case Study - Creatine, Phosphocreatine, and ATP. (n.d.). Retrieved from http://learn.quinnipiac.edu/at/faculty/hs/alsmith/creatine_phosphocreatine_atp.html

[8] Cooper, R., Naclerio, F., Allgrove, J., & Jimenez, A. (2012). Creatine supplementation with specific view to exercise/sports performance: an update. J Int Soc Sports Nutr, 9(1), 33. http://www.jissn.com/content/9/1/33

[9] Creatine Supplementation in Athletes: Review. (n.d.). Retrieved from http://www.rice.edu/~jenky/sports/creatine.html

[10] Creatine: MedlinePlus Supplements. (n.d.). Retrieved from https://www.nlm.nih.gov/medlineplus/druginfo/natural/873.html

[11] Powers, M. E. (2003). Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution. Journal of Athletic Training, 38(1), 44-50. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC155510/

[12] Syrotuik, D. G., & Bell, G. J. (2004). Acute creatine monohydrate supplementation: A descriptive physiological profile of responders vs. nonresponders. Journal of Strength and Conditioning Research, 18(3), 610–617. https://doi.org/10.1519/12392.1

[13] SYROTUIK, D. G., & BELL, G. J. (2004). ACUTE CREATINE MONOHYDRATE SUPPLEMENTATION. Journal of Strength and Conditioning Research, 18(3), 610-617. http://journals.lww.com/nsca-jscr/Abstract/2004/08000/Acute_Creatine_Monohydrate_Supplementation_.39.aspx

[14] MIHIC, S., MacDONALD, J. R., McKENZIE, S., & TARNOPOLSKY, M. A. (2000). Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medicine & Science in Sports & Exercise, 32(2), 291. doi:10.1097/00005768-200002000-00007

[15] PEETERS, B. M., LANTZ, C. D., & MAYHEW, J. L. (1999). Effect of Oral Creatine Monohydrate and Creatine Phosphate Supplementation on Maximal Strength Indices, Body Composition, and Blood Pressure. Journal of Strength and Conditioning Research, 13(1), 3-9. doi:10.1519/00124278-199902000-00001

[16] Safdar, A., Yardley, N. J., Snow, R., Melov, S., & Tarnopolsky, M. A. (2008). Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiological Genomics, 32(2), 219-228. doi:10.1152/physiolgenomics.00157.2007

[17] Parise, G., Mihic, S., MacLennan, D., Yarasheski, K. E., & Tarnopolsky, M. A. (2001). Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. Journal of Applied Physiology, 91(3), 1041-1047. doi:10.1152/jappl.2001.91.3.1041

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