Hello Rob,

Nicely formulated question, but you got me right where it hurts, the lack of published scientific studies addressing creatine’s solubility and degradation in aqueous solutions. Below is what I have been able to piece together from the literature that I have been able to find. Other reports surely exists, I have simply not been able to pin them down.

Since one of your queries uses the term, thermodynamics, I use this approach to answer the question. Don’t worry. I’ll try and develop the answer in an intuitive manner, not like a university physical chemistry course.

Ok, buckle-up, here we go…

What Is Creatinine?

Creatinine is the degradation product of creatine, the very popular muscle-building supplement. Creatinine is produced (from creatine) inside the cell, in the blood stream, in your glass of creatine before drinking, or on the shelf in your creatine container. Basically, creatine will spontaneously convert to creatinine in almost any environment you can image. The pertinent issue here isn’t whether creatinine will be produced, but rather under what conditions will it be produced in the greatest amounts to effectively dilute out creatine?

So, Why Should I Care if my Creatine Becomes Creatinine?

Unlike creatine, which fuels muscular movement, creatinine does not donate energy to muscle. Creatinine is hence energetically useless to muscle. Nor is creatinine actively taken up and concentrated within the muscle cell in the same way that creatine is. Once creatine is transported into muscle moreover, it becomes trapped inside. In fact, the only way for creatine to escape from muscle is for to be converted into creatinine; creatinine is then able to freely diffuse through the muscle membrane to the outside. Since greater amounts of creatine within muscle translates into more creatinine escaping into the blood stream, blood creatinine levels can be used as an indirect measure of muscle creatine content.

Creatine Degrades in Water to Produce Creatinine

Water facilitates the conversion of creatine into creatinine. This chemical reaction (known as intramolecular cyclisation) takes place at room temperature (and atmospheric pressure, etc.) independently of any other participants besides creatine and water. Hence, it occurs spontaneously under a variety of real world conditions.

A schematic of this reaction can be found at the following link:
http://www.creatinemonohydrate.net/illustrations-reactions

Under typical life conditions, however, we needed worry about the reverse reaction – the conversion of creatinine into creatine. So, let’s ignore its possibility.

What Does Thermodynamics Have to do With it?

The Second Law of Thermodynamics states that nature tends towards disorder, a state known as Entropy. Entropy is the preferred state of any system. For instance, a house of cards built on top of a table is a much more ordered state than the same number of card scattered over the floor; entropy favors the latter process.
Now, since creatinine is about ten-times more soluble than creatine it disperses more readily in water and increases the “randomness” of the system (your glass, cup, or container of creatine solution) when it is produced – an entropic benefit.

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In essence, the system is more “comfortable” (at a lower energy state) when many smaller molecules of creatinine are produced from a fewer insoluble clumps of creatine monohydrate. In fact, both the breakup of a few creatine clumps into a greater number of individual creatine molecules as well as their later conversion into many mobile creatinine molecules help satisfy this “Entropic drive” – the need of our universe to increase disorder.

I hope this all makes sense; from here on out it gets much more practical. I promise.

Why the “Thermo” in Thermodynamics?

Adding energy to the system increases the rate at which any favored reaction occurs. Going back to our house of cards analogy, a slight breeze may be all the energy it takes to blow the house over - entropy takes care of the rest. Initially, the cards interact with each other in a stable way. However, even the slightest perturbance is enough to disrupt these interactions and bring down the structure.

Concerning creatine, extra energy pushes the reaction forward towards the formation of creatinine, assisting in the creation of disorder. One way to add energy to the system is to heat the solution. At room temperature (approximately 25 degrees Celcius) creatine converts to creatinine at a rate of only about 3%-7% per day – 0.1% to 0.3 % per hour. Heating it up to 50 degrees Celcius, on the other hand, speeds up degradation rate anywhere between 20- and 40-fold, depending on starting conditions – 2% to 4% per hour. Still, this is not an enormous amount of creatine being lost due to warm temperatures.

Take Home: Simply warm your creatine solution enough so that it is comfortable to drink immediately after mixing it thoroughly. In other words, don’t nuke your creatine solution in the microwave for 10 minutes and then let it stand for 20 minutes before you can drink it…

Upcoming Post: On the other hand, heating also counteracts the relatively high insolubility of creatine monohydrate, effectively offsetting the negative consequences of any increase in creatinine production with high temperatures. How to establish conditions that optimize creatine solubility while at the same time minimize creatinine production will be discussed in my upcoming post.