Friday, April 18, 2014

Is Creatine Smart?

by Alfredo Franco, PhD

Those of you familiar with my writings are well aware of the fact that I am strongly in support of intelligent training methods. In this article, I give this advocacy a unique twist and discuss whether it is possible to train for intelligence. Research has shown that a person’s cognitive capacity may remain acute far into advanced age, if practiced throughout life. In a sense, this result suggests that a person’s “mental fitness” improves with training. And since, nutritional supplements plays a big role in modern athletics, this issue also begs the question whether nutritional supplementation may also help maintain mental fitness. In this respect, a pivotal study recently appeared in the scientific press that examined the effects of creatine supplementation on human intelligence (1). This study might change the way you think…

Brain Energetics

As for any activity we undertake, thought requires energy-or should, in any case. In fact, thinking takes lots of energy. On a per weight basis, the brain is one of the body’s highest energy consumers. Although representing only 2% of our total body mass, the brain consumes nearly one quarter of our entire energy resources. The disproportionate amount of energy consumed by our brains is reflected by the fact that the head is generally warmer than the body core temperature; this gives an entire new meaning to the phrase “hot head”, doesn’t it.

Any thought we abstract, any sensation we perceive, or any action we initiate, is encoded by electrical impulses that literally flow throughout our nervous systems. However, unlike the electrical currents that flow through the wires in our homes and that are carried by negatively charged electrons (a part of an atom), the electrical impulses that propagate through our nerve cells, or neurons, are largely mediated by positively charged atoms that, interestingly enough, lack electrons. Such charged atoms are known as ions, nothing more than atoms with an incomplete number of electrons in their outer shell. Electrical currents (carried by positive ions) literally flow through our neurons relaying information from brain to target, and back again.

A neuronal impulse is initiated with the flow of positively charged sodium ions into a neuron. This influx of sodium ions causes a localized accumulation of positive charges near their point of entry at the neuronal membrane. To relieve this buildup of positive charges, potassium ions (also positively charged) respond by flowing outward, since like charges repel each other. This instantaneous switch in ionic polarity can be likened to a spark that rapidly spreads along the entire length of the nerve cell. Obviously, this situation cannot continue forever, otherwise all of the sodium ions would end up on the inside the neuron and all the potassium ions on the outside. Indeed, after a flurry of electrical activity the relative distribution of sodium and potassium (near the membrane) nearly reverses. In order for brain activity to continue, therefore, these ions need to be actively placed back onto their appropriate sides of the membrane. This process is energetically very expensive.

The molecular pumps that are responsible for situating sodium and potassium back to their respective sides of the neuronal membrane are called ATPases; obviously, since they rely on ATP to function. In fact, maintaining these pumps active is the greatest sink of energy in the brain. As in muscle, however, ATP is often limiting. Also analogous to the muscular situation is the fact that phosphocreatine (PCr) is what assures a steady supply of ATP to the cell. PCr thus keeps these ATPases pumping sodium and potassium back into their respective compartments, thereby allowing continual neuronal activity. Figuratively speaking, phosphocreatine keeps us thinking.

So, what does this have to do with creatine?

Recall that PCr is the energized form of creatine that is present within the cell. When we supplement with creatine, what we are in actuality doing is increasing the PCr content of the cell. Therefore, at least in theory, creatine supplementation should influence how well we think under pressure. Food for thought, so to speak. One recent study, furthermore, showed that mice deficient in the enzyme that creates PCr from creatine, creatine kinase, are slower at learning a water maze (2). In other words, the mice with lower levels of PCr erred more often and generally spent more time in the water. The stage was thus set for human studies…

Does creatine supplementation influence mental acuity in humans?

This was the question asked by a recent study conducted at the Universities of Sydney and Macquarie, Australia.

Study Design:

The study examined the effect of creatine supplementation (5 grams/day for six weeks) on the ability to perform two cognitive tests, the Raven’s Advanced Progressive Matrices (RAPMs) and Weschler Auditory Backward Digit Span (BDS). These tasks are designed to test non-verbal intelligence (IQ) and verbal memory capacity (short-term memory), respectively.

The authors of the study also chose 45 vegetarians and vegans as experimental subjects. This group of individuals was specifically chosen since their dietary intake of creatine, which was negligible, would not interfere with the amount of creatine administered during the course of the study.

This study consisted of a placebo-controlled, cross-over design. This simply means that each subject served as his own control scenario. Subjects either took creatine or placebo (maltodextrin) for six weeks before performing one of the mental tests (week 6). They then washed out for another six weeks in order that their creatine levels should return to baseline (week 12). Supplementation then commenced anew (six more weeks) using the opposite supplementing condition. During the 18th week they then repeated the same test under the influence of the second supplementing condition. The entire cycle repeated after a washout of another six weeks with the other mental task. Therefore, each subject took each test twice, once under the influence of creatine and once under the influence of placebo.

Study Results:

Subjects who were administered creatine exhibited improved short-term memory and were also better able to problem solve under pressure of time. Specifically, the creatine group was better able to repeat back long sequences of numbers from memory (BDS). Creatine subjects were on average able to repeat back 1-2 more integers than placebo counterparts. Their general IQ scores were also higher than the placebo group (RAPMs). Quoting directly from the manuscript: “Supplementation with creatine significantly increased intelligence compared with placebo”.

Take Home:

So, should you take a teaspoon of creatine before your next all-nighter? Although “thought provoking”, it’s still too early to say. Not all thought processes are alike. This study does seem to suggest, however, that creatine may help with complicated computational tasks.

Who knows, in the future taking a swig of creatine before a cram session may be an accepted practice among university students.

Scientific References

1. Rae, C., Digney, A .L., McEwan, S.R. & Bates, T.C. (September 2003) Oral creatine monohydrate supplementation improves cognitive performance; a placebo-controlled, double-blind cross-over trial. Proceedings of the Royal Society of London – Biological Sciences. Volume 270(1529): pages 2147-2150.

2. Jost, C. R., Van Der Zee C. E., In’t Zandt H. J., Oerlemans F., Verheij M., Streijger F., Fransen J., Heerschap A., Cools A. R. & Wieringa B. (May 2002) Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility. European Journal Neuroscience Volume 15 (10): pages 1692-706.

This article was written by Dr. Alfredo Franco, research scientist, author, and owner of the Creatine Information Center and NSN Publishing.

Dr. Franco has had over 20 years of in depth research experience in major laboratories world-wide. His principal scientific interest is the understanding of the cellular mechanisms leading to muscle cell death.

Dr. Franco is also the author of Creatine: A practical guideCreatine: A practical guide clearly teaches you how to best combine exercise, nutrition, and intelligent creatine use for optimal muscle growth, improved athletic performance, and overall good health. Find out more about this must-read book.

This article is copyrighted material. Unauthorized reproduction of this article is strictly prohibited. Contact us for posting rights.


Copyright 2013 © NSN Publishing

Wednesday, April 16, 2014

The Creatine-Insulin Dilemma

by Alfredo Franco, PhD

Creatine is, by no means, new to this world. Creatine is, and always has been, a natural constituent of skeletal muscle. Humankind simply needed to be made aware of its existence. Amazingly, creatine was first identified nearly two centuries ago! In the early 1800s, the French scientist and philosopher, Michel-Eugène Chevreul, isolated a novel agent from skeletal muscle that he later named creatine for kreas, the Greek word for flesh (1).

A few years later (1847), a German scientist named Justus von Liebig observed that maintaining foxes in captivity decreased their muscular creatine content (2). Postulating that physical activity increases creatine uptake by skeletal muscle, Liebig advanced the hypothesis that muscles utilize certain nitrogen containing molecules for energy. These nitrogenous molecules, otherwise known as amino acids, include creatine. Intriguingly, as an extension of his findings, Liebig later lent his name to a commercial extract of meat, which he asserted would help the body perform extra “work”. In fact, “Liebig’s Fleisch Extrakt” could quite reasonably be considered the original creatine supplement (complete with marketing plan). Near the turn of the last century the first studies examining the effects of creatine feeding were conducted where it was noticed that not all the creatine fed to animals could be recovered in the urine. Soon afterwards, Otto Folin and W. Dennis (1912-1914) of Harvard University (Boston) unequivocally corroborated by that the body’s musculature retains the greater part of any ingested creatine.

Therefore, nearly one century ago scientists had already come full circle, from discovering that skeletal muscle is the richest natural source of creatine to the largest sink for dietary creatine in the body. Nevertheless, up to quite recently, the manner in which to best promote creatine absorption by skeletal muscle remained largely elusive. In this respect, a huge leap forward was made with the finding that insulin assists in the absorption of creatine into skeletal muscle. And, although this effect was previously hinted at in animal studies, the studies that first clearly showed this effect in humans were conducted only a few years ago (3,4). These human studies used glucose to stimulate the production of insulin, the same agent used by the body for this same purpose.

Following a meal our blood glucose levels rise, which then serves as the signal for the release of insulin from the pancreas. Insulin, in turn, enables the cells of our body to take up nutrients, principally glucose, but also amino acids, from the blood stream. Creatine, due to its structural likeness to amino acids, is also transported into the cell with the assistance of insulin, although via a different transport pathway. In this respect, insulin sets the stage for muscle growth (aka, anabolism) by making available to the cell the basic substrates for the production of new muscle tissues.

The problem with the original studies examining insulin-mediated creatine uptake in humans, however, was that the amounts of glucose required to evoke a strong enough release of insulin were exorbitant; nearly 20 grams of glucose for each gram of creatine consumed and close to the limit of palatability for most individuals. Furthermore, this amount of glucose, if consumed on a regular basis, could lead to a state of insulin-resistance, which is the path to the development of type II diabetes. In other words, cells become immune to the presence of insulin if constantly bombarded by it, which, in turn, diminishes the uptake of essential nutrients into muscle cells and increases the need for insulin to stimulate muscle growth. Furthermore, since fats cells are the last to become resistant to the effects of insulin, the initial stages of insulin-resistance causes our fat reserves to swell and our muscle mass to shrivel up. Therefore, although these results were promising, they were far from being a complete solution.

Since then, there has been a search for agents that might effectively release insulin into the blood stream (for the purpose of creatine adsorption) without adversely influencing insulin-sensitivity. Many creatine manufacturers have consequently taken to adding a variety of insulin-agonists to their products in hopes of getting around the insulin-dilemma. These “insulinotropic” strategies are aimed at either enhancing the release of insulin from the pancreas or augmenting the effects of upon the cell in order to increase transport rates of creatine into skeletal muscle. The agents often used for this purpose include chromium picolinate, alpha-lipoic acid, 4-hydroxyisoleucine, and the amino acids, taurine, L-arginine, NO-releasers, and L-carnitine. These days it is quite common to find one, or more, of these agents in many creatine products. Unfortunately, with the exception of alpha-lipoic acid (5), none of these agents have been specifically shown in scientific studies to potentiate the uptake of creatine into the cell. This in time may come, but for the moment, it’s still too early to say whether these other agents actually promote creatine absorption by muscle cells.

There’s a safer, and much more reliable, method of promoting insulin release that has been overlooked by many creatine manufacturers. Ignored, in fact, simply because it isn’t sexy enough to appear innovative and, consequently, will not serve to jack up the price of the product; the agenda of most creatine manufacturers. By now, the ability of glucose to release insulin is without dispute. Ten years ago, however, a study showed that protein greatly potentiates the ability of glucose to release insulin into the blood stream from the pancreas (6). The effect of protein was so powerful that half the amount of carbohydrates could be used to elicit the same amount of insulin release.

What remained to be shown was whether the combination of carbohydrates and protein is equally as effective at promoting creatine absorption by skeletal muscle. This awaited study finally appeared in 2000 and showed that protein in combination with simple carbohydrates augments creatine absorption by skeletal muscle to a similar extent as high doses of carbohydrates (7). In this study experimental subjects were given one of four different supplement combinations 30 minutes after ingesting creatine, 5 grams of glucose (placebo), 50 grams of protein and 47 grams of glucose (PRO-CHO), 96 grams of glucose (Hi-CHO), or 50 grams of glucose (Lo-CHO). The results were clear, PRO-CHO and Hi-CHO were equally effective at promoting creatine absorption, which were both greater (~10-25%) than either Lo-CHO and placebo. Again, adding protein reduced the glucose requirement by half!

Another advantage of adding glucose to your creatine is that it aids in the replenishment of your glycogen reserves following exercise. This effect arises from the ability of insulin to increase the number of glucose transporters (GLUT 4) expressed on the cell surface. GLUT 4 is the principal protein complex responsible for transporting glucose into the cell once stimulated by insulin. And, since exercise makes the cells of our body more sensitive to the effects of insulin, exercise likewise increases the expression of GLUT 4. On the other hand, inactivity, either by choice or because of injury, reduces GLUT 4 expression.

Along these lines, a recent study has shown that creatine protects against the loss of GLUT 4 during limb immobilization and, furthermore, accentuates the increased expression of GLUT 4 during subsequent rehabilitation (8). Not surprisingly, the creatine and glucose treated subjects exhibited larger muscle glycogen (and creatine) reserves during rehabilitation. Finally, a new study just appeared indicating that protein exerts a similar effect on GLUT 4 expression, but without adversely affecting insulin-sensitivity (9). Specifically, this study compared the effects of creatine supplementation with glucose or glucose plus protein during the rehabilitation of a previously immobilized limb. The authors of this study found that retraining (6 weeks) a previously immobilized limb (2 weeks placed in a cast) in conjunction with a post-exercise creatine, protein and glucose meal increased GLUT 4 expression and muscle glycogen content to the same extent as a creatine and glucose meal. Most importantly, since the protein meal contained less than one third the amount of glucose (20 grams versus 70 grams!), insulin sensitivity was improved as a result. Furthermore, the effect on glycogen storage was specific for the exercised limb. That is, the un-exercised limb exhibited no change in GLUT 4 expression or muscle glycogen content. This result clearly indicates that simply upplementing with creatine, irrespective of the manner in which it is done, in the absence of exercise is a fruitless endeavor.

The solution seems clear. Adding protein to your creatine and carbohydrate mix will promote muscle creatine uptake (and glycogen synthesis) WITHOUT adversely affecting the sensitivity of your cells to insulin.

Author’s Note: Due to space constraints, other very important anabolic benefits of combining protein and creatine were not covered in this article. These other anabolic attributes, and how to best make use of them, are discussed in my creatine guide. Click here for more information about the guide.

Scientific References

1. Chevreul, X. (1835) Sur la composition chimique du bouillon de viandes. J. Pharm. Sci. Accessoires Volume 21: pages 231-242.

2. Balsom, P. D., Soderlund, K. and Ekblom, B. (1994) Creatine in humans with special reference to creatine supplementation. Sports Medicine Volume 18: pages 268-280.

3. Green, A. L., Simpson, E. J., Littlewood, J. J., MacDonald, I. A., and Greenhaff, P. L. (1996). Carbohydrate ingestion augments creatine retention during creatine feedings in humans. Acta Physiol Scand Volume 158: pages 195-202.

4. Steenge, G. R., Lambourne, J., Casey, A., MacDonald, I. A., and Greenhaff, P. L. (1998). Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. American Journal of Physiology Volume 275: pages E-974-E979.

5. Burke, D. G. Chilibeck P. D., Parise G., Tarnopolsky M. A., and Candow D. G., (2003). Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. International Journal of Sports Nutrition and Exercise Metabolism Volume 13(3): pages 294-302.

6. Chandler, R. M., Byrne, H. K., Patterson, J. G., and Ivy, J. L. (1994). Dietary supplements affect the anabolic hormones after weight-training exercise. Journal of Applied Physiology Volume 76(2): pages 839-845.

7. Steenge, G. R., Simpson, J., and Greenhaff, P. L. (2000). Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. Journal of Applied Physiology Volume 89: pages 1165-1171.

8. Op’t Eijnde, B., Urso, B., Richter, E. A., Greenhaff, P. L., and Hespel, P. (2001). Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes Volume 50: pages 18-23.

9. Derave, W. Op’t Eijnde, B., Verbessem, P., Ramaekers, M., Van Leemputte, M. Richter, E. A., and Hespel, P. (2003). Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans. Journal of Applied Physiology Volume 94: pages 1910–1916.

This article was written by Dr. Alfredo Franco, research scientist, author, and owner of the Creatine Information Center and NSN Publishing.

Dr. Franco has had over 20 years of in depth research experience in major laboratories world-wide. His principal scientific interest is the understanding of the cellular mechanisms leading to muscle cell death.

Dr. Franco is also the author of Creatine: A practical guideCreatine: A practical guide clearly teaches you how to best combine exercise, nutrition, and intelligent creatine use for optimal muscle growth, improved athletic performance, and overall good health. Find out more about this must-read book.

This article is copyrighted material. Unauthorized reproduction of this article is strictly prohibited. Contact us for posting rights.

Copyright 2013 © NSN Publishing

Thursday, April 03, 2014

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