Oxygen is potentially toxic, a seemingly counterintuitive statement, since common knowledge tells us that we need oxygen to live. Specifically, without oxygen we would not be able to produce energy from basic nutrients and would die….

So, how can oxygen be toxic?

Oxygen is an Electron Sponge

Nothing is perfect. The exact same property that makes oxygen a benefit to the cell, makes it a danger to the cell, its ability to absorb electrons.

Oxygen: The Benefit

The removal of electrons by oxygen is an essential step in the “oxidation/combustion” of foods. In biochemical terms a nutrient is nothing more than a collection of Carbon-Hydrogen bonds that can be broken to release electrons - electrons, in turn, are energy. During cellular respiration the cell uses these freed electrons to create its own energy molecule, a molecule called ATP (Adenosine TriPhosphate).

Take a look at the molecular structure of ATP here:

http://www.creatinemonohydrate.net/Illustrations-reactions

Unaccompanied Electrons Are Also Dangerous…

Once the electrons have been used to create ATP they need to be discarded from the cell. Otherwise they would raise havoc by interacting with unsuspecting cellular components. This is where oxygen comes in; in the best of conditions, oxygen removes these electrons from the cell as soon as they are freed and in the process forms water.

Oxygen: The Danger

What transforms oxygen from a cellular benefit to a detriment is a reduction in the efficiency with which it absorbs electrons. Oxygen becomes “reactive” when it is unable to absorb its full capacity of electrons and is left half satisfied, figuratively speaking. Sloppy electron absorbance is most common when the rate of oxygen utilization increases dramatically.

Question:

Under what circumstances would we need to increase our rate of oxygen utilization?

Answer:

During exercise…

Exercise increases the need to break down nutrients to produce enough energy to maintain strenuous physical activity. The greater the rate of nutrient combustion, the greater the use of oxygen, the sloppier the process of electron transfer becomes and unfortunately, the greater number of Reactive Oxygen Species, or ROS, that are produced. ROS are also a form of “free radical”.

The Remedy

Fortunately, the body has come up with ways to combat ROS production. The body’s ROS defense mechanisms include a battalion of molecules known as antioxidants, whose job is to molecularly stabilize ROS (by converting them back into oxygen and water) immediately upon their production.

The body produces it own antioxidants from proteins such as Superoxide dismutase, Catalase and Glutathione as well as obtains them from the diet in the form of vitamins A, C and E. When the rate of nutrient combustion (oxidation) increases dramatically, however, the body’s oxidative defense mechanisms cannot keep up and ROS damage occurs. This has led to many athletes taking antioxidant vitamins to defend against free radical damage and potentially, over training syndrome.

Do Antioxidant Vitamins Actually Reduce Free Radical Damage During Exercise?

Next time I’ll discuss a study that examined the ability of vitamin antioxidants (taken in capsular form) to combat oxidative stress (ROS neutralization) during exercise. The results of this study were rather surprising and relevant to anyone taking vitamins A, E, or C to combat oxidative stress during exercise.

In brief, the study suggests that antioxidant supplementation does not improve our ability to defend against free radical damage during exercise. Don’t despair, however, there is still room for an alternative interpretation of these results.

Until next time…

Creatine’s Insolubility Causes Problems

One of the most problematic aspects of dietary supplementation with creatine monohydrate powders are their poor solubility - this annoying feature gives rise to a range of inconveniences ranging from not being able to get your creatine into solution to persistent diarrhea.

Heating Increases the Amount of Creatine That Goes Into Solution

Although this may sound like a contradiction it is not. Recall from the last post that heat increases the disorder of our “creatine in a glass” system, which translates into more creatine molecules being randomly dispersed (dissolved) in our liquid. In fact, increasing the temperature increases the solubility of creatine in water significantly. In practical terms, going from 10 to 50 degrees Celsius increases the solubility of pure creatine monohydrate about three-fold. This is an important consideration, since creatine is rather insoluble; typically about 14 grams of pure creatine monohydrate can be dissolved in a liter of water at room temperature (25 degrees Celsius). Importantly, this values drops to around only 8 grams of creatine being able to be dissolved in one liter of water right out of the refrigerator (4 degrees Celsius). And, of course, creatinine production will also increase, although much less significantly than the increase in creatine solubility. Can you see where I am going with this?

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Your Creatine Still Won’t Dissolve??

If you are still having problems getting all your creatine into solution, then maybe you are adding too much powder, or have too little liquid in which to dissolve it. At room temperature you should be able to dissolve around 7 grams of creatine per 16 ounces of water (approximately 0.5 liter). Heat the solution to 50 degrees Celsius (warm) and you should be able to increase this amount to around 17 grams per 16 fluid ounces, or about 5 grams in 5 fluid ounces. This is more than enough creatine to ingest at one time for most athletes.

The maximal amount of creatine that is absorbable by a human being is explained in my creatine guide. Go to the follow link for more information about the guide: http://www.creatinemonohydrate.net/creatineguide

So, is it pointless to heat your creatine solution before taking it?

It is a tradeoff, as most things are in life. Fortunately, this one issue has a clear upside. Here is my reasoning…

While it is true that heating your solution of creatine monohydrate will increase the rate that it converts into creatinine, the rate of degradation (conversion into creatinine) is relatively small - only of the order of a few percent after a few hours. This represents only a relatively minor change in functional creatine content. On the other hand, heating your creatine solution will significantly increase the amount that goes into solution, which, in turn, will alleviate certain forms of gastrointestinal discomfort as well as increase the amount of creatine that can be absorbed into the blood stream from your digestive tract.

Take Home

Go ahead and heat up your creatine solution to assist in dissolving it, but drink it almost immediately afterwards and don’t overdo it with the heating. If you can drink it comfortably within a few minutes of mixing it, the temperature should be ok and the degradation of creatine (to creatinine) should be minimal.

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.

A version of this question appeared in my inbox a few days ago. I felt it important enough to merit its own post in this blog. Today, I’ll post the original question and in a few days I’ll upload my answer.

Sincerely,
Alfredo Franco-Obregón
Nutritional Supplements Newsletters Publishing
http://www.creatinemonohydrate.net
http://www.creatine-blog.com

Question

Following is a question regarding “Creatine Solubility” that I haven’t seen addressed within the contents of your website and the answer to which could prove to be of great value and interest not only to myself but to all your readers & visitors to this website. I have yet to receive a fair & comprehensive answer to my question from any other sources which is why I’m now turning to you for help.

Greetings Dr. Franco-Obregón:

I’d like to start things off first by offering to you my heart felt “Thanks” for your website and its mission of … [offering to us (the public) frank, candid & unbiased information, separating fact from fiction, & truth from all the hype] … and also for all you do to accomplish that end! I’ve found it (your website) to be very informative, helpful & educational. Please keep up the “Great” work! In appreciation to the value of your time, I’d like to extend to you a couple of incentives for giving my question priority, the first of which is listed above in that I have yet to discover the issues surrounding my question being currently addressed within the content of your website. I do believe that other readers and visitors to this site would find great value and interest in the answer to my question and with this in mind, I’d like to suggest that rather than responding directly to this email (alone) with your answer, that you would address it in the form of a new article to be added to your current article list for others to enjoy and learn from also. My second incentive for giving my question priority is that if it’s answered to my satisfaction (with clinical study & scientific data references included) I will then purchase your Ebook “Creatine: A practical guide.” I’d like to preface my question with a little background information. I’m a frequent guest/visitor of the website BodyBuilding.com and while reading through a fair number of their articles about creatine supplementation I came across the following 2 statements from differing articles and I quote…

“Dissolve your creatine in a warm beverage. By doing so, due to the laws of thermodynamics, the creatine is solubilized. And when consumed, it can be absorbed much more effectively without all the GI distress.”

“The practice of cooking actually reduces the amount of creatine in meat; the heating converts some of the creatine to its breakdown product called creatinine.”

Now on to my question…

There appears to be somewhat of a contradiction or conflict between these 2 statements…in one it says to dissolve in a warm beverage whereas another discusses how when creatine is heated, this heating process converts or breaks down some of the creatine into “Creatinine.” Granted, cooking meat is subjecting its creatine content to a much more intense form/level of heat than would be realized from a “Warm” beverage and I’m sure this plays a huge role in any differences found in the time frame that it takes for the creatine to be broken down into its “Creatinine” byproduct when placed in these respective environments i.e., “Warm Beverage” vs. “Meat being cooked.” But this leads me to my questions…

1. What are these “Time-Frame” differences in how long it typically takes for creatine to be broken down into creatinine when subjected to heat (heat meaning, warmer than say room
temp.?)

2. Are there any “Studies” to your knowledge that have been done addressing these issues, primarily, if creatine is placed in a warm/hot beverage for consumption, how long will it take before it begins to be broken down into “Creatinine?”

3. Or any “Studies” that do a comparison between differing temperature variables vs. the amount of time for “Break Down?” So for example, “At room temp, it will take X amount of time, at 90 degrees it will take X amount, at 100 degrees X amount etc. etc. right on up the line all the way to typical cooking type temps?”

For example again, one of the quotes listed above mentions how when creatine is mixed with water or other fluids, some of the creatine will “Eventually” start to convert to creatinine. I’m assuming then that when additional heat is applied or introduced it will speed up this conversion/break down process. So it would be nice to know how long I have (what kind of time frame) when I mix my creatine with a heated cup of water (to increase its solubility and make its absorption more effective) how long or how much time do I have (in case I’ve made the water a little to hot for chugging purposes and need to let it cool down a bit) to consume it before it begins to lose its effectiveness due to being broken down or converted into creatinine because of the heat? It sounds to me as though there’s a fine line/balancing point in here somewhere. On one hand, you’re trying to make it more soluble to improve its absorptive qualities thereby making its uptake more effective … and then on the other hand, you could be losing or trading in some of that gained effectiveness because of the “Heat” issue and how that factor increases or speeds up the degradation process into creatines worthless byproduct… “Creatinine.” I look forward to your reply and I thank you in advance for your time and consideration regarding my questions and these issues!

Sincerely,
Rob Etnyre!!!

Stay tuned for the answer to this question in a few days….

Bones and Teeth are Calcium Reservoirs

Nearly all (99%) of our entire calcium allotment resides within the structural matrix of bones and teeth. As such, our bones serve as a reserve source of calcium in moments of dietary deficiency. This function of bones is principally under the control of two hormones, one vitamin and stomach acid:

• First, parathyroid hormone prompts bones to release calcium into the blood stream, weakening their internal structure at the expense of providing calcium for global cellular needs.
• Calcitonin, on the other hand, is a hormone that causes bones to absorb calcium (when available) from the blood stream.
• Vitamin D plays a role in calcium acquisition by increasing the amount of calcium that is transported across the intestinal wall into the blood stream.
• Stomach acid also promotes calcium absorption into the blood stream. Stomach acid ionizes calcium, increasing its solubility and accentuating its transport across the intestinal wall.

Calcium Insufficiency Weakens Bones

Calcium insufficiency results in bone frailty, a condition known as osteoporosis (porous bone). Ironically, an age-related decline in stomach acid production contributes to the predominance of osteoporosis in the elderly by slowing calcium absorption into the blood stream (see last point above). To complicate matters further, caffeine’s diuretic nature also diminishes the amount of calcium that is available for absorption from the intestine by increasing the rate of its excretion from the body. The elderly, especially women, should avoid heavy caffeine consumption due to its adverse effect on calcium uptake from the digestive tract.

Calcium Transport Consumes Creatine Energy

Mechanistically, calcium absorption recruits the activity of special transporters (Calcium-ATPases) on the surface of the cells forming the intestinal-blood barrier. These transporters use energy (derived from creatine) to actively pump calcium into the blood stream from the intestinal compartment. It was thus a logical assumption that creatine availability should also influence the efficiency of calcium transport from the intestinal space into the blood stream. And indeed, this turned out to be the case. Several studies have shown that creatine augments calcium transport across isolated preparations of intestinal membranes by fueling the activity of these calcium transporters. What remains to be shown is that ingested creatine has this same calcium-pumping effect in the guts of alive animals. Nonetheless, via such a mechanism, creatine supplementation should benefit those at risk of developing osteoporosis.

Learn about other benefits of creatine supplementation for the elderly at the following links:
http://www.creatinemonohydrate.net/creatine_elderly.html
http://www.creatinemonohydrate.net/creatine_sarcopenia.html

Take home

In the last series of posts I gave three examples where creatine supplementation would promote bone strength. This is an important effect since muscle and bone strength must increase in parallel for optimal athletic performance. In the first post I showed that the increased levels of muscular force afforded by creatine supplementation serves to stimulate bone fortification. Secondly, I gave evidence that creatine itself serves as an anabolic stimulus for the creation of new bone. That is, the mere exposure of bone cells to creatine, even in the absence of mechanical stimulation by muscles, stimulates them to produce bone matrix. This mineralization process, however, relies largely on the presence of calcium. Therefore, in today’s post I discussed a physiological mechanism whereby creatine supplementation may augment calcium absorption from the digestive tract into the blood stream. Calcium availability is often the bottleneck in bone maintenance in the elderly and in certain diseases. I therefore suggest that the elderly take proactive measures to assure that they obtain sufficient amounts of creatine in the diet to help maintain bone health in later life.

How the elderly can best acquire dietary creatine is explained in my guide:
http://www.creatinemonohydrate.net/creatineguide

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