A compilation of creatine studies...

[B.A.]

...Accumulated through a host of different strength discussion forums and websites. I certainly found reading through some of them to be most interesting. Please view objectively:

VIII. CREATINE SIDE EFFECTS: An interview with Professor Jacques R. Poortmans

Background
Dr. Jacques Poortmans of the Free University of Brussels in Belgium is one of the world's foremost creatine experts. His articles examining the consequences of creatine supplementation have appeared in many of the premier sport medicine journals. For this issue of the Creatine Newsletter I was fortunate to be able to interview Dr. Poortmans. I’m sure you’ll find it as enlightening as I did.

NSN: A common concern is that creatine supplementation places undue stress on renal function. Is there any truth to this?

JRP: No, as long as renal functions are normal before any creatine supplementation. We, and others, have given published evidences that in healthy individuals short-term, medium-term and long-term oral creatine monohydrate supplements are safe for the kidney. Of course, one has to be certain that the product is PURE (by analysis) since there are, apparently, many commercial products which do not satisfy the quality imposed by the FDA.

NSN: It is known that creatine absorption by our muscles decreases dramatically after a week of loading and that afterwards most of the ingested creatine is cleared from the body by the kidneys. Given this information, is there harm any in extending the loading phase past one week?

JRP: No, if one respects the loading doses: about 20 grams per day for 5 days and thereafter a 2-3 gram doses per day. One has to know that about 60% of the ingested doses are not taken up by the muscles and are cleared into the urine. What a waste of money!

NSN: What effect does creatine monohydrate have on liver function?

JRP: None. Again, we and others did not observe any impairment of liver tests after oral creatine supplements in healthy subjects (men and women).

NSN: Who should avoid creatine use? Diabetics who are predisposed to renal complications, for example?

JRP: Certainly those patients as well as anyone suffering from ANY kidney impairment. Heavy creatine supplements still remain an extra load on the renal filtration process.

NSN: Is taking creatine with protein a mistake?

JRP: Recent investigations by us and another research team did not observe a difference between creatine alone or creatine protein as far as muscle composition is concerned. What seems important is to provide enough daily protein intake (about 1.2-1.3 g/kg body weight, no more) to sustain protein synthesis.

NSN: I often get asked about secondary sexual side-effects associated with creatine use. As far as you know is there any basis for this concern?

JRP: There is no reason to believe that there is a relationship between creatine and sexual behavior (or capability). But, as usual, it might be of some help for those who sentimentally believe in anything. However, as said before, be careful with the purity of the product. We know that some commercials add anabolic steroids to creatine. This conduct cannot be tolerated. Excess anabolic steroid substances can have negative effects on sex and general health care

 

[B.A.]

Effects of creatine on isometric bench-press performance in resistance-trained humans.
Kilduff LP, Vidakovic P, Cooney G, Twycross-Lewis R, Amuna P, Parker M, Paul L, Pitsiladis YP.
Centre for Exercise Science and Medicine, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.

PURPOSE: The purpose of this study was to investigate the effects of creatine (Cr) supplementation on force generation during an isometric bench-press in resistance-trained men. METHODS: 32 resistance-trained men were matched for peak isometric force and assigned in double-blind fashion to either a Cr or placebo group. Subjects performed an isometric bench-press test involving five maximal isometric contractions before and after 5 d of Cr (20 g.d-1 Cr + 180 g.d-1 dextrose) or placebo (200 g.d-1 dextrose). Body composition was measured before and after supplementation. Subjects completed 24-h urine collections throughout the study period; these were subsequently analyzed to provide total Cr and creatinine excretion. RESULTS: The amount of Cr retained over the supplementation period was 45 +/- 18 g (mean +/- SD), with an estimated intramuscular Cr storage of 43 (13-61) mmol x kg(-1) x dry weight muscle (median [range]). Four subjects in the Cr group were classified as "nonresponders" (< or =21 mmol x kg(-1) x dry weight muscle increase following Cr supplementation) and the remaining 17 subjects were classed as "responders" (> or =32 mmol x kg(-1) x dry weight muscle). For the Cr group, peak force and total force pre- or post-supplementation were not different from placebo. However, when the analysis was confined to the responders, both the change in peak force [Repetition 2: 59(81) N vs -26(85) N; Repetition 3: 45(59) N vs -26(64) N) and the change in total force (Repetition 1: 1471(1274) N vs 209(1517) N; Repetition 2: 1575(1254) N vs 196(1413) N; Repetition 3: 1278(1245) N vs -3(1118) N; Repetition 4: 918(935) N vs -83(1095) N] post-supplementation were significantly greater compared with the placebo group (P < 0.01). For the Cr group, estimated Cr uptake was inversely correlated with training status (r = -0.68, N = 21, P = 0.001). Cr significantly increased body weight (84.1 +/- 8.6 kg pre- vs 85.3 +/- 8.3 kg post-supplementation) and fat-free mass (71.8 +/- 6.0 kg pre- vs 72.6 +/- 6.0 kg post-supplementation), with the magnitude of increase being significantly greater in the responder group than in the placebo group. CONCLUSION: Five days of Cr supplementation increased body weight and fat-free body mass in resistance-trained men who were classified as responders. Peak force and total force during a repeated maximal isometric bench-press test were also significantly greater in the responders compared to the placebo group.

PMID: 12131259 [PubMed - indexed for MEDLINE]

 

[B.A.]

Creatine and Injury Recovery

Background
Mature skeletal muscle is produced from the union of progenitor cells known as myoblasts. These myoblasts lie dormant waiting for the appropriate environmental cue to stimulate them to fuse. One of the most potent of such environmental cues is the loss of muscle tissue arising from inactivity or disease. To summarize, lost or damaged muscle is replaced by new muscle formed from the fusion of thousands of myoblasts.

The loss of muscle tissue because of inactivity or disease is known clinically as disuse atrophy. Anyone who has had a broken limb can testify to this effect. After weeks in a cast the immobilized limb is noticeably smaller and weaker than its unrestrained counterpart. In this instance inactivity resulted in muscle tissue actually being reabsorbed by the body. When the limb again becomes active the body replaces this lost muscle tissue through a process known as myogenesis.

Myogenic factors
Although muscle loss induces the process of regeneration, the actual triggering signal is a biochemical messenger. These biochemical messengers, also known as myogenic factors, were the focus of a recent study involving creatine.

The Study
This study examined the effect of creatine supplementation on the recuperation of muscle function following leg immobilization. Twenty-two college-aged subjects participated in the study. All subjects had their right leg immobilized in a cast for a period of two weeks. Ten weeks of rehabilitation therapy followed the two weeks of cast immobilization.

Throughout the entire study half of the subjects took creatine while the other half took placebo (maltodextrin). During the two weeks of immobilization the subjects supplemented their daily diets with 20 grams of either creatine monohydrate or placebo. During the rehabilitation period the creatine/placebo dose was reduced. For the initial three weeks of rehabilitation the subjects consumed 15 grams of creatine/placebo per day. Thereafter, the creatine dose was reduced to only 5 grams of creatine/placebo for the remaining seven weeks of rehabilitation.

Cross-sectional area of the quadriceps muscle (upper leg), leg extension power and myogenic factor expression were compared in the two groups.

Results
This study demonstrated that leg cross-sectional area and strength recovered more rapidly in those individuals who had supplemented with creatine.

Most importantly, myogenic factor expression was greater for the creatine group during the rehabilitation phase of the study. In particular, one myogenic factor, MRF4 (Myogenic Regulatory Factor 4), correlated strongly with the increase in leg cross-sectional area. It would thus appear that MRF4 is responsible for the muscle regeneration observed in this study. Interestingly, MRF4 exerts its greatest effect over those muscle fibers most sensitive to creatine supplementation; the fast muscle fibers.

Conclusions
This study concluded that creatine supplementation stimulates muscle growth and recovery through the production of myogenic factors, in particular one known as MRF4. The authors of the study openly state that "creatine supplementation is capable of shortening the duration of rehabilitation needed to restore muscle mass following an episode of disuse atrophy".

Take Home
This study suggests that creatine increases the expression of myogenic factors that induce muscles growth.

 

[B.A.]

Creatine and Women From MuscleChem

Background
The short answer is "yes". The long answer is also "yes, but differently from men". Creatine supplementation has two well-documented effects. The first is that creatine increases our muscle energy reserves, allowing us to train harder. The second is that creatine induces muscle swelling through increased water retention, increasing our body mass and size. Interestingly, this second effect, also known as muscle volumizing, might cause our muscles to actually amass proteins. Unfortunately, since most creatine studies have focussed on males (18 and 35 years of age), it wasn't clear whether creatine benefits females in the same way.

Study #1: Peter Hespel, Belgium
In 1997 Peter Hespel's group in Belgium showed that creatine supplementation enhances muscle energetics in females. This effect was similar to the previously demonstrated effect in males that depends on an increase in muscle phosphocreatine levels.

Design
The sample group consisted of 19 healthy, but sedentary females. Their ages ranged from 19-22 years. Half of them took creatine tablets, while the other half took maltodextrine tablets. The creatine group commenced supplementation with a loading phase of 20 grams of creatine per day for five days, followed by a maintenance phase of 5 grams of creatine per day for a period of 10 weeks. This was a relatively long-term study.

Results
Strength increased by ~20% and fat-free mass increased by ~60% in the creatine group. These values were similar in magnitude to those previously described in male subjects. In addition, this study found that creatine supplementation maintained strength for an additional 10 weeks after training had stopped.

Conclusion
Creatine increases fat free mass and repetitive exercise performance in women. Creatine also appears to enhance exercise performance when not accompanied by training.

Study #2: Mark Tarnopolsky, Canada (Hot Off the Press!).
This September Mark Tarnopolsky's group in Toronto published a study comparing the turnover rates of proteins in males and females in response to creatine supplementation. Motivated by the finding that fat-free mass increases following creatine use, these authors sought to determine if this effect is solely due to increased muscle hydration or whether increases in muscle protein content also contribute. They were also interested in determining whether creatine supplementation benefits males and females to the same extent.

Design
The sample consisted of 13 males and 14 female subjects. On average they were 23 years of age. They were asked to abstain from taking any other supplements during the study period. The design was similar to the previous study. Half of the subjects (males and females) were given placebo; the other half were loaded with 20 grams of creatine monohydrate powder a day for 5 days, followed by a maintenance dose of 5 grams of creatine for a period of 3-4 days. This was a short-term study.

Results
This study found that while the rate of new protein production did not change in response to creatine use, the rate of protein degradation decreased. It thus appeared that creatine suppressed protein degradation. In scientific jargon this would be known as an "anti-catabolic" (anti-breakdown) effect and would eventually lead to greater protein levels in supplementing individuals. This effect would also contribute to the increase in fat-free mass commonly observed with creatine use. Unfortunately, while this protein-sparing effect was apparent in males, it was virtually absent in females. The reason for this gender disparity is currently unresolved.

Interestingly, muscle creatine (and phosphocreatine) levels increased to the same extent in both males and females, explaining why fat-free mass also increases in both sexes. Remember that water follows creatine into skeletal muscle resulting in muscle volumizing and consequently in an increase in fat-free mass. In other words, the relative proportion of fat to total muscle mass, including water, decreases with creatine use. This increase in fat-free mass, however, is typically less pronounced in women, which also makes sense since the protein sparing effect of creatine is virtually absent in women.

Conclusion
This study concluded that creatine supplementation spares proteins from being degraded. Furthermore, the authors hypothesized that this was an effect downstream of muscle volumizing and is supported by experiments showing that infusing males (through their veins) with dilute saline (to induce cell swelling) exhibited similar protein sparing effects. In other words, cell swelling induced without creatine also spares proteins from being degraded. Therefore, this effect has little to do with creatine per se.

Take Home
Creatine enhances exercise output and lean muscle mass in both males and females. Furthermore, creatine may also spare the breakdown of proteins as a result of strenuous exercise. This effect appears to be more pronounced in males than in females. The reason for this disparity is still an open issue, but may involve the different hormone environments typical of males and females.

 

[B.A.]

CREATINE AND FAT

Background
It is common knowledge that creatine causes weight gain. The reason for this gain in weight seems to involve several distinct processes. Early phases of body mass increase involve the retention of water into skeletal muscle. Later phase of mass increase may involve the accretion of new muscle proteins.

Early Stages of Muscle Growth: Water Weight
Creatine monohydrate causes water to be retained in the body compartments where it is located. For this reason our muscles swell (with water) following creatine use. This process has been termed muscle "volumizing" in the scientific literature. This is a relatively fast process and can account for as much as 1-3 kilograms (~2-7 pounds) of added water weight after just a few days of loading. This increase in weight is much too fast to be attributed to the addition of new muscle proteins. Finally, since the faster we pack in creatine, the faster we'll gain water weight, muscle volumizing will be most pronounced during the loading phase.

After about a month of stopping creatine our muscle creatine stores return to normal and so should our body weight. In other words, we'll lose muscle water as our creatine levels return to their previously low values.

We'll also notice a drop in our energy levels. This is because creatine enhances our physical performance by increasing the amount of energy available to our muscles.

Later Stages of Muscle Growth: New Protein Production
There is some indication that the acquisition of new muscle proteins also increases following creatine supplementation. This effect might be related to the greater work capacity afforded by creatine. In other words, we'll build more muscle since we'll be able to train harder.

Alternatively, muscle volumizing itself might stimulate the production of new muscle proteins. In this instance muscle swelling might falsely signal to the cell that it is growing. The muscle cell might then respond by increasing the production of new muscle proteins. The likelihood of this later possibility is currently being debated in the scientific press.

Any increase in muscle proteins as a result of prolonged creatine use should persist after stopping supplementation. These gains, however, will be relatively small in comparison to the initial rise in body weight attributed to water retention.

Lean Muscle Mass
The combined effects of increased muscle hydration and stimulated protein synthesis will increase our amount of lean muscle. In other words, the amount of protein and water contained within our muscles will increase relative to fat. You might have heard this fact being boosted in the popular press.

Fat is Fat and Muscle is Muscle and Never the Twain Shall Meet
It has often been rumored that a person's muscle turns to fat after stopping creatine. There is no more truth in this happening than there is in an apple turning into a banana? They are simply two different entities. Nevertheless, muscle can be replaced by fat given the wrong set of circumstances.

As mentioned above, after stopping creatine you'll lose some size due to loss of muscle water. You'll also experience a drop in energy level because of the slow degradation of surplus creatine stored within our muscles; remember that creatine is an energy source.

There's only one way you'll gain fat. That is if you reduce your energy expenditure dramatically, or stop working our altogether, while not adjusting your caloric intake. Under these circumstances the excess amounts of calories (food) you consume will be stored as fat.

Take Home
You will lose some size and strength after stopping creatine. This is unavoidable. The lost size, however, results from loss of water and not muscle tissue. The decrease in energy results from less creatine in our muscles. The only way that you will gain fat is if you consume more calories than you burn after stopping creatine.

Therefore, after stopping creatine for a prolonged period, be sure to maintain your exercise intensity, or alternatively, reduce caloric intake.

 

[B.A.]

Effect of creatine loading on neuromuscular fatigue threshold.
Stout J, Eckerson J, Ebersole K, Moore G, Perry S, Housh T, Bull A, Cramer J, Batheja A.

Exercise Science Department, Creighton University, Omaha, Nebraska 68178, USA. jrstout@creighton.edu

The purpose of this investigation was to determine the effect of creatine (Cr) loading on the onset of neuromuscular fatigue by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at the fatigue threshold (PWC(FT)) test. Using a double-blind random design, 15 women athletes [mean age 19.0 +/- 2.0 (SD) yr] from the university crew team received a placebo (n = 8; 20 g glucose) or Cr (n = 7; 5 g Cr monohydrate + 20 g glucose) four times per day for 5 consecutive days. Analysis of covariance was used to analyze the data (covaried for presupplementation PWC(FT) values). The adjusted mean postsupplementation PWC(FT) value for the Cr group (mean = 186 W) was significantly (P < 0.05) higher than that of the placebo group (mean = 155 W). These findings suggest that Cr loading may delay the onset of neuromuscular fatigue.

PMID: 10642369 [PubMed - indexed for MEDLINE]

 

[B.A.]

Creatine and Fat Loss

Background
Obviously, creatine finds its way into skeletal muscle after being ingested. But, how is this process actually accomplished?

From the blood stream creatine is transported into skeletal muscle via the action of transporter molecules distributed along the muscle surface. These are the molecular doors that allow creatine into muscle cells. Our physiological status determines how well these molecular doors work at letting in creatine. For example, the amount of sodium outside the muscle cell, the extramuscular sodium, regulates the activity of these transporter molecules. In this respect, an elevation of extramuscular sodium promotes creatine entry via these transporters.

Based on earlier studies showing that caffeine increases extramuscular sodium, it was proposed that caffeine should augment creatine transport into muscle cells and accentuate the benefits of creatine. Oddly, however, caffeine has the opposite effect than initially expected. Caffeine actually interferes with the enhancement of physical performance afforded by creatine. A possible explanation for this paradoxical finding is the topic of this month's newsletter.

The Study
A recent study specifically looked at the consequences of caffeine consumption on the physical benefit normally afforded by creatine supplementation. The study consisted of a cross over design, which simply means that the subjects were divided into either experimental (caffeine and creatine) or control (creatine alone) groups, tested after a week, switched of conditions and then retested.

Nine males participated in the study. Their ages ranged between 20 and 23 years. Initially both groups were given 0.5 grams of creatine/kilogram of body weight for six days. This amount is slightly greater than the typically prescribed loading dose. In addition, the experimental group was also given 0.005 grams of caffeine per kilogram of body weight on days 4, 5 and 6. Therefore, for the last three days of supplementation the experimental group consumed both creatine and caffeine. On the seventh day their physical performance was tested using knee extension torque measurements. This is one entire day after the last dose caffeine.

After a washout period of 3 weeks the groups were switched, such that the experimentals (caffeine and creatine) became controls (creatine alone) and visa versa. The experiment was repeated. In this respect the effect of caffeine could be compared within each individual.

The Result
Caffeine consumption negated the physical benefit observed in the creatine group. Surprisingly, the effect of caffeine was observed one entire day after the last dose. This finding was at first paradoxical, because caffeine, at least initially, was proposed to increased creatine absorption into skeletal muscle via its effect on extramuscular sodium.

The amount of caffeine used in this study is equivalent to 2-3 strong cups of coffee for an average sized male, or 350 mg of caffeine for a 70 kilogram (154 pound) male. One important detail might be that caffeine was administered in the form of capsules.

Interestingly, caffeine did not interfere with the rise in muscular phosphocreatine associated with creatine loading. Remember that phosphocreatine is the biologically active form of creatine found within cells. In other words, caffeine neither decreased (nor increased, as expected) creatine transport at the muscle surface. Its inhibitory effect was felt after creatine had entered and formed phophocreatine.

A Possible Resolution
Coordinated movement is the result of opposing muscle groups contracting and relaxing in unison. For example, when performing a curl our biceps (front of arm) contract into a ball, whereas our triceps (back of arm) relax and lengthen. On the downward movement, the triceps contract and the biceps relax.

Another example is sprinting. A sprinter initiates a stride by contracting the front muscles and relaxing the back muscles of one leg. To move forward, however, he must then quickly relax the front muscles and contract the back muscles of that leg, so that his other leg can shoot forward. Therefore, muscle relaxation is part of coordinated movement and thus speed.

Calcium is what causes muscles to either contract or relax. A muscle contracts when calcium is released from storage sites deep inside the muscle. In other words, free calcium is the signal that tells a muscle to contract. Likewise, our muscles relax when calcium is reabsorbed into these internal storage sites. However, the restorage of calcium is an energetically expensive process and in this manner muscle relaxation cost us energy. The energy that pays for muscle relaxation comes from phosphocreatine!

Dr. Hepel's group in Belgium has elegantly shown that phosphocreatine levels determine muscle relaxation rate. When our muscle phosphocreatine levels are high, as a result of supplementation, our muscles relax more rapidly. Conversely, when our phosphocreatine stores are low, muscle relaxation is slowed and our exercise performance drops.

Although caffeine doesn't alter phosphocreatine levels, caffeine may nevertheless retard muscle relaxation by altering muscle calcium levels. Interestingly, caffeine is known to release calcium form internal stores. As outlined previously, this would slow muscle relaxation and jeopardize exercise performance, despite caffeine's know stimulatory properties. Therefore, caffeine may negate creatine's benefit by liberating internal calcium and thereby slowing muscle relaxation time.

False Rumors
Caffeine is a diuretic, meaning that it increases the excretion of water from the body in the urine. There are rumors that caffeine counteracts creatine by interfering with muscle volumizing. This is simply a false rumor and assumes that water retention by skeletal muscle is the source of strength. Although increasing the girth (volume) of our muscles, volumizing per se has no proven effect on strength. This was the topic of a recent newsletter. View it here.

Take Home
If you pump up on caffeine prior to working out, while at the same time supplementing with creatine monohydrate to increase exercise performance, you could be wasting your time and money. Avoid this practice!

However, it must be mentioned that not all studies demonstrate an inhibitory effect of caffeine on the benefits afforded by creatine and may be a result of how creatine was administered, ie whether in liquid or tablet form.

 

[B.A.]

Creatine Fact & Fiction by Layne Norton


I don't usually like to write whole articles about supplements because I believe diet and training to be far more important than any combination of supplements. However there are a few supplements that work, creatine being the most notable of all of them. It is the best selling supplement ever, period. Creatine sales totaled over 100 million dollars in last year alone! These sales were to everyone from middle scholars to the elderly. With this recent rush of creatine madness there has also been a wave of misinformation. I cannot believe the things I hear people say about creatine's effectiveness, about how it works, and about it's safety. There is some information floating around out there that is just untrue, well never fear, I am here to combat misinformation so here it goes.



What is it?



Creatine is a combination of three different amino acids, glycine, arginine, and methionine. That's it, it is nothing more than a combination of amino acids. I don't know how many people I hear talk about creatine and call it a steroid! I almost flip my lid when I hear it. Steroid? If that were the case it there would be a lot more 200+ pound people out there.

No creatine is not a steroid, it is totally different and works in a different manner. Creatine is also produced by the body and found in high protein sources of meat such as fish and red meat. It is NOT a lab synthesized compound, it is natural.



How Does it Work?


After creatine enters the body (or after it is produced by the body) it firsts binds with a phosphate molecule to form Creatine phosphate. Now here is where I'm going to lay a bit of biochemistry on you so I'll do my best to keep it simple. ATP (Adenine Tri-Phosphate) IS the body's energy source. When your body oxidizes carbs, protein, or fat it is doing this process in order to produce ATP. ATP is responsible for driving almost every body process there is. Hell ATP is even involved in creating ATP. ATP works like this... Energy is needed to drive bodily process. ATP provides this energy by hydrolyzing a phosphate group.


When a phosphate group is hydrolyzed, energy in the form of heat is given off and this energy is used to drive whatever process is being performed, for example muscle contraction. Because one phosphate has been lost from the ATP it is now called ADP (adenine Di-phosphate). The reaction is as follows ATP (hydrolysis)=ADP + Energy. Now you have free ADP as a product from the ATP hydrolysis. ADP is pretty much useless in the body unless it is converted back into ATP. Now this is where creatine comes into play. The phosphate bound creatine donates it's phosphate group to the ADP to re-form ATP! I assume you see where this is going now. By allowing you to return ADP to ATP creatine will increase your ATP stores, thus allowing you to train harder and longer.Creatine is a combination of three different amino acids, glycine, arginine, and methionine.

Another benefit of creatine is that creatine itself is a fuel source. In fact your body's first choice of energy when performing anaerobic activity (such as weightlifting) is your creatine phosphate stores. By supplementing with creatine phosphate you will increase these stores, thus giving you more energy for your workouts. There is another anabolic property that creatine holds and this is it's ability to hydrate muscle cells.1 When muscle cells are hydrated a few things happen. The most notable being an increase in protein synthesis.
The second being an increase of ions into the cell. Since the cell is holding more water, it can also hold more ions since the ions will follow water into the cell in order to keep the concentration the same. When more ions are present in muscle cells (the most important being nitrogen) muscle protein synthesis also increases.



How Safe is Creatine?


Since creatine has only been recently introduced to the market it is hard to determine whether or not there will be long term health effects from it's use. However it must be noted that to date there is not one, I repeat not one reputable study that shows creatine has any dangerous side-effects. 2 After eight years with no severe side effects I believe that one can begin to assume that creatine is relatively safe. I find it funny that most people I meet that are concerned about creatine's safety are also people who like to go out and drink and smoke on weekends...try to find the irony in that.



Is it Necessary to Load on Creatine?


No it is not necessary to load but it can help you see results faster. You see to get the full benefit of creating you must saturate your muscle cells with it. Using a small dose (5g), this will take up to thirty days depending on the individual's lean body mass. However using a loading dosage of 15-25g per day for 5 days, one can quickly saturate the muscle cells in this time period and then use a maintenance dosage (3-5g) for the remainder of their time taking creatine. (Recent research shows that a loading phase longer than 3 days is useless - Icex999)



Is it Necessary to Cycle Creatine?


Once again it is not necessary to do so but it can help. Your body has an internal equilibrium which you can swing in your favor for a duration of time, but over time that equilibrium will eventually swing back.
Meaning taking excess creatine for a short period of time (4-8 weeks) may temporarily increase your creatine phosphate stores but after awhile your body's feedback mechanisms will likely place some time of control on creatine phosphate storage to bring the levels back down to normal. This mechanism may be to decrease your body's own production of creatine or to downgrade the number receptors that admit creatine into the cell. Taking time off from creatine can help bring your body's equilibrium back into a state where in taking excess creatine will be beneficial again. I would like to make clear at this point that I know of no studies to back this theory up with, it could be right or wrong, I am just merely applying my knowledge of biochemistry to a frequently asked question to which there is no good answer to yet.



What is the Best Time to Take Creatine?



There has been much discussion on this but I believe taking creatine post workout is the most beneficial time for several reasons. Insulin helps drive more creatine into muscle cells, if you are a smart bodybuilder then in your post workout meal you should be eating foods that help spike your insulin, if this is the case, then taking creatine with this meal will help it's uptake into muscle cells. The body absorbs many nutrients better after a workout. Creatine will help refuel your body's low creatine phosphate stores.
Will Taking Creatine Before a Workout Give Me More Energy?
No, not exactly. Once again for creatine to work your muscle cells must be saturated with it. This takes at least a week to do, so doing it once before a workout will not make a difference. Now if your cells are already saturated with creatine then it will still not make a difference if you take it before you workout. Your body must process it first and that takes time. The creatine your body will use in the upcoming workout will come from the creatine phosphate stores already in the cells, not from the creatine you just ingested.



Does Liquid Creatine Work?


Most certainly not. Creatine degrades over time in water into it's waste product creatinine which is useless in the body and will simply be excreted. Companies who claim that they have stabilized creatine in a liquid are flat out lying to you. One of these companies (I believe Muscle Marketing USA) had a lab assay done on their liquid creatine and the assay found that it only contained 15% of the creatine on the label claim. I would like to further de-credify these companies by noting that one of the reasons they claim their product is so good is because their creatine does not make your retain water. WHAT? As I have stated earlier, this is one of the biggest benefits of creatine, this clearly shows their eagerness to prey upon the ignorance of the public.



What is the Best Type of Creatine?


Well if you want the most bang for your buck do not buy the creatine transports! These are enormously overpriced and you can make them yourself at half the price by buying your own dextrose online! A little tip... a mix of 50g whey protein and 50g dextrose has been shown to elicit the same insulin spike as a serving of Cell-Tech, and it is much cheaper I might add.


References

1. Stoll B, Gerok W, Lang F., Haussings. Liver Cell Damage and Protein Synthesis.
Biochemical Journal 287 (Pt 1) 217-222, 1992.

2. Kreider et. al. Perceived Fatigue Associated With Creatine Supplementation During the
Fall Collegiate Baseball Series of Division I Players. Journal of Athletic Training.
April-June 2001 v31 i2 pS 83.

 

[B.A.]

CAN CREATINE REDUCE MUSCLE DAMAGE?

Background
Muscle damage is a natural consequence of exercise. A small amount of muscle damage is not a terrible thing. In fact, small amounts of muscle damage actually stimulate new muscle growth, which is good. However, if the extent of muscle damage exceeds our body’s capacity to repair it and rebuild, we’re in big trouble. We then have a scenario of net muscle breakdown, otherwise known as catabolism, which defeats the whole point of working out and is a huge waste of time, money and effort.

Two principal forms of muscle damage arise from physical exertion. The first is mechanical and occurs immediately. In other words, our muscles tear slightly during the physical stress of exercise. The second form of muscle damage is the result of chemicals that are released during exercise and that exert their degenerative effects a few days later.

Free Radicals
Now, for more details on the second type of muscle damage. Intense exercise produces what are known as Reactive Oxygen Species, or ROSs for short. One of the most dangerous of the ROSs is the Superoxide Radical. Even sounds dangerous! Our body normally has the capacity to neutralize Superoxide as soon as it is produced.

How is Superoxide Produced?
Superoxide is produced from oxygen. Heavy breathing during intense exercise increases the rate of Superoxide production and surpasses the body’s capacity to neutralize it. This gives rise to a situation known as oxidative stress.

Superoxide weakens the muscle membrane causing it to tear. These small tears allow muscle’s contents to leak out and calcium ions to seep in. Importantly, an unregulated increase in intramuscular calcium activates enzymes that cause the muscle cell to self-destruct. Obviously, something we want to avoid.

Antioxidants
Our bodies contain a line of defense against oxidative stress; special molecules known as antioxidants that neutralize ROSs. Vitamins A, C and E are examples of vitamin antioxidants. Vitamin E is a particularly potent antioxidant that protects our cellular membranes from degradation following oxidative stress. Some studies suggest that the vitamin antioxidants can reduce exercise-induced muscle damage. Our bodies also come equipped with their own antioxidant molecules. Some of the most important are Superoxide Dismutase, Glutathione Peroxidase and Catalase.

Eating foods rich in antioxidants and getting plenty of rest increases our body’s capacity to deal with oxidative stress.

Is Creatine an Antioxidant?
Very recently (January 2002) a study was released suggesting that creatine might act as a Superoxide scavenger in its own right. It is therefore possible that part of the benefit we obtain from creatine derives from its capacity to act as an antioxidant.

The salient points of the study are as follows:

1. The concentration of creatine used in this study was within physiological limits. In other words, comparable to that found within skeletal muscle (20-60 mM, for those who are interested). This gave relevancy to the study.

2. Creatine is a mild antioxidant. Creatine was not as effective as Glutathione at scavenging free radicals

3. Creatine’s ability to neutralize Superoxide was measured in a test tube, not an exercising person.

Take Home
This preliminary report seems to suggest that creatine possess' antioxidant properties and can effectively neutralize Superoxide, one of the more insidious free radicals produced by exercise. However, since these findings where obtained in a test tube, it remains to be shown if creatine has the same effect in an exercising person. Although preliminary, this result is surely provocative and worth pursuing.

Scientific Reference
Lawler JM, Barnes WS, Wu G, Song W, Demaree S. (January 2002) Direct antioxidant properties of creatine. Biochemical and Biophysical Research Communications. 290: 1: pages 47-52.

 

[B.A.]

CREATINE AND GROWTH HORMONE

Since creatine increases our exercise capacity, and exercise increases hormone release, it is expected that creatine should also indirectly increase the amounts of anabolic hormones produced while exercising. Indeed, one recent study has possibly demonstrated this predicted effect. Surprisingly, however, in this study Growth Hormone release was observed in non-exercising subjects after ingesting creatine. In other words, just taking creatine was sufficient to increase Growth Hormone production.

The Study: Six males were given a breakfast of 20 grams of creatine monohydrate dissolved in a half-liter of hot water. They were then told to limit their activity (but not fall asleep!) for the rest of the morning. For six hours their blood was monitored at intervals for the presence of creatine and Growth Hormone. As expected, blood creatine levels rose within minutes of taking creatine monohydrate. Blood Growth Hormone levels, on the other hand, required about 2 hours before rising. This lag indicates that the release of Growth Hormone depends on other cellular events occurring first. Growth Hormone increased on average ~80% over baseline values. Albeit provocative, this finding needs to be viewed with caution until corroborated by other studies.

What are the implications of this study?
This study suggests that creatine may have an anabolic property independent from its ability to increase exercise intensity. This result may also explain why some studies have shown that muscle cells raised in "tissue culture" (out side of the animal in plastic dishes) increase their production of muscle proteins when exposed to creatine. As were the subjects in the previously mentioned study, these muscle cells were inactive due to their growth conditions.

Another unexplained observation is why creatine appears to be less effective in the elderly. This situation may be partially explained by the decline in Growth Hormone levels in the aged. In other words, part of the benefit of creatine might be absent in elderly persons with less Growth Hormone. Time will tell if these assumptions are right. We'll just have to wait.

Problems with the Study
Firstly, since these experiments were conducted on a relatively young (~23 years of age) and healthy set of subjects, it is not known whether these findings also apply to the elderly and ill.

Secondly, the sample size was small (six) and the individual responses to creatine varied widely. Three showed strong increases in Growth Hormone levels, two had moderate to low increases in Growth Hormone, and one showed no increase. This variability in Growth Hormone release is somewhat reminiscent of the situation of nonresponders to creatine. In fact, the authors of the study postulated that such differences in Growth Hormone release might underlie creatine-nonresponsiveness.

Finally, the amount of creatine used in the study was comparable to a typical loading dose - taken all at once! This practice is not recommended to the general product.

Unanswered Questions
1. Are other anabolic hormones similarly influenced by creatine?
In this study it was not determined whether other anabolic hormones, such as testosterone or insulin, similarly increase with creatine use.

2. What about Insulin-Like Growth Factor?
Many of the effects of Growth Hormone are mediated by Insulin-Like Growth Factor 1 (IGF-1), which the liver produces when stimulated by Growth Hormone. Interestingly, IGF-1 has also been shown to enhance creatine uptake into isolated muscle cells. Could this work in a feed-forward manner? In other words, does IGF-1-induced creatine uptake, further enhance Growth Hormone release.

3. What is the cellular signal that triggers Growth Hormone release?
Growth Hormone levels increase a few hours after creatine levels do. The biologically active form of creatine is phosphocreatine, creatine to which a phosphate group has been attached. Could phosphocreatine be the signal that triggers the release of creatine from the Anterior Pituitary in our brains?

Take Home
Creatine enhances exercise performance in most young and healthy individuals. Since exercise induces the release of anabolic hormones, creatine supplementation should also, in theory, indirectly increase the release of Testosterone, Insulin and Growth Hormone during exercise. This study suggests that creatine by itself (in the absence of exercise) may suffice to trigger the release Growth Hormone by the body. This finding is intriguing and might explain the previously unexplained increase in protein synthesis in isolated muscle cells not undergoing activity. Furthermore, if Growth Hormone mediates part of the effect of creatine supplementation, then this study might also explain why creatine supplementation is often less efficacious in the elderly, which have reduced Growth Hormone levels. In conclusion, this study suggests that creatine supplementation may have anabolic properties independent of its effect on energy metabolism. Future scientific investigation will tell if this finding is valid.

 

[B.A.]

Creatine and Side Effects


This is clearly the most frequently asked question about creatine. Understandably, the risks associated with the use of creatine monohydrate concerns many. Numerous side effects have been attributed to creatine use. Some of these side effects have been substantiated in the scientific literature while other side effects have not. Most of the side effects associated with creatine have to do with its propensity to draw water into body compartments where it is located, namely the intestine and skeletal muscle. As a result dehydration is a real concern while supplementing with creatine. Drink at least 1 ounces of water per pound of bodyweight while taking creatine.

Is creatine safe for women, children, the pregnant or the elderly?

Children:
Whether creatine is safe for children (preadolescents) is our secondly most frequently asked question. Naturally, what are creatine's side effects is the first. Since the long-term consequences of creatine supplementation are not well understood, it is best to avoid supplementation during childhood. Furthermore, a recent panel of creatine experts has concluded that creatine may be less effective children.

Elderly:
Interestingly, this same panel of experts also suggested that creatine may be less effective in the elderly (greater than 70 years of age). Changes in muscle fiber composition (or mass) may underlie any difference in creatine-sensitivity in the elderly.

Women:
The vast majority of creatine studies have been conducted on males between the ages of 18 and 35 years old. Nevertheless, a couple of studies have also demonstrated enhanced exercise performance in women supplementing with creatine, which actually makes sense since creatine's basic mechanism of action wouldn't be expected to differ in women. Nevertheless, differences do exist in how creatine benefits men and women.

Pregnancy:
Since it is not known whether creatine levels increase in breast milk following supplementation, creatine use should be avoided in nursing women.

Volumizing:
Weight gain is the most commonly reported creatine side effect. As much as 3 kilograms (6.6 pounds) of increased weight within the first few weeks has been reported in response to creatine use. This is due mainly to the movement of water from the blood into skeletal muscle. This form of muscle growth has also been termed Volumizing because of the increase in muscle volume that ensues. This side effect may be beneficial in certain sports such as, body building, but be less desirable in other sports such as, distance running or other endurance sports. Also see dehydration.

Dehydration:
It's imperative to remain well-hydrated while taking creatine. This concern is valid since much of our body water follows creatine into skeletal muscle, possibly depriving our remaining tissues of fluid. As a consequence urine output often decreases during creatine supplementation. Down the road this may lead to impaired thermoregulation and subsequent heat exhaustion, especially if training heavily in hot environments. This precaution is especially important in combative sports (in particular, wrestling) where athletes strive to make weight before competition. Weight loss under these circumstances is often achieved through fluid restriction which, in combination with creatine use, could lead to excessive dehydration.

Gastrointestinal Distress:
Reports of gastrointestinal distress, stomach cramps, nausea and diarrhea have also been attributed to creatine use, especially when taken in large doses. These side effects are most likely due to undissolved creatine drawing water into the intestine and can often be circumvented by completely dissolving creatine in at least 16 ounces of water or juice. The large amounts of sugars often taken with creatine may also complicate gastric emptying. These side effects are rarely observed when taking smaller doses of creatine.

Muscle strains, cramps and tears:
There have been reports of muscle pulls, strains and cramps following creatine use. These injuries may be related to an electrolyte imbalance as a result of dehydration. Drink plenty of fluids while taking creatine!

Renal Stress:
There is also some concern that creatine supplementation may place undue stress on the liver and kidneys. These concerns are most valid when creatine is taken is large quantities. For example, during the loading phase. Under these conditions the kidneys would have to work harder to clear unabsorbed creatine from the blood stream; there is much more creatine in the urine of person's consuming large amounts of creatine. Persons with pre-existing kidney disorders should probably abstain from creatine use.

Blood Pressure:
There was some concern that the fluid retention as a result of creatine use could increase a person's blood pressure. This issue was recently a topic of a scientific study that found that blood pressure did not increase following 5 days of creatine use.

Cholesterol and Protein Synthesis:
Creatine may have some positive side effects. For example, creatine may improve our cholesterol levels independently of its effect on exercise. In addition, volumizing may in itself stimulate the production of new muscle proteins. Both these effects, however, need to be further substantiated by additional scientific research.

Rumors:
There are many misconceptions and rumors surrounding creatine use. Most of these stem from creatine being wrongly associated with hormonal means of increasing muscle mass. These unsubstantiated side effects include breast formation in men, a reduction in penis size, hair loss in men, hair growth in women and stunted growth in children. Unexplained incidences of aggression and acne have also been linked to creatine use. Furthermore, some of these unexplained side effects may arise from other agents taken with, or in addition to, creatine. To reiterate, creatine increases exercise performance at the level of muscle energetics. Creatine does not substantially alter hormone levels to induce muscle growth, such as is the case with anabolic steroids.

Long term consequences of creatine use?
Since it is a realtively recent practice very little is known of the long term consequences of creatine use. However, some of its alleged side effects may have long term ramifications, especially at the elevated doses typically prescribed for athletics. For example, the time required for transporter function to fullly recover after prolonged exposure to elevated creatine levels is simply not known for humans. This is why creatine we do not advise creatine use for children or pregnant women (see ABOVE).

There are, however, clinical situations for which low doses of creatine have been used over a period of years with no signs of adverse side effects. For example, Gyrate Atrophy is a disease of the eye (retina) that is characterized by progressive narrowing of the visual fields. A secondary component of the disease is a deficiency in creatine synthesis. Consequently, this disease is also characterized by a reduction in the size of fast muscle fibers (see Question #5). Creatine supplementation has been shown to alleviate the muscular symptoms associated with this disease although the visual symptoms persist. Of interest to us; other than mild weight gain, low doses of creatine (1.5 grams/day) when administered for the duration of a year produced no obvious adverse effects.

Does creatine cause cancer?
There has recently been alot of talk about the possible risk of creatine causing cancer. The concern arises from the fact that certain cancer causing agents (AIAs) are produced when meat is cooked at high temperatures. The production of these cancer causing agents correlates with the initial creatine (and creatinine) content of the meat; meats with higher creatine content produce more of these cancer causing agents when cooked. It has thus been hypothesized that by increasing our muscle creatine content, we also increase our chances of getting cancer. It remains, however, to be clearly demonstrated that these same cancer causing agents are produced within the animal under physiological conditions. In other words, in an animal that isn't cooked this effect of creatine may not be manifested.

Finally, since creatine increases the growth rate of some types of tumor cells, it has been suggested that creatine may increase our chances of getting cancer. However, other experiments shows no effect of creatine on tumor cells. Whether creatine has a similar effect on normal cells is still an open issue.

Is it true that creatine might help those with Muscular Dystrophy?
Creatine has been used in clinical trials for several classes of Muscular Dystrophy. Our muscles can become weakened as a result of injury or disease. This is the case for several forms of Muscular Dystrophy. Although creatine would not be expected to cure Muscular Dystrophy, creatine supplementation may improve the quality of life of persons experiencing muscle weakness as a result of these diseases. In fact, preliminary studies have indicated that creatine supplementation improves strength in those inflicted with certain forms of Muscular Dystrophy as well as other Neuromuscular disorders. For more information see the Muscular Dystrophy Association's "Answers to frequently asked questions about creatine".

 

[B.A.]

Effects of Long Term Creatine Use

Long Term Creatine Use
Is creatine safe?

Title: Effects of Long-term Creatine Supplementation on Liver and Kidney Functions in American College Football Players.

Researchers: Mayhew DL, Mayhew JL, Ware JS

Institution: Exercise Science Program at Truman State University, Kirksville, MO 63501 and the Athletic Department at Truman State University, Kirksville, MO.

Summary: The purpose of this study was to determine the effect of long-term Cr supplementation on blood parameters reflecting liver and kidney function.

Methods: Twenty-three members of an NCAA Division II American football team (ages = 19-24 years) with at least 2 years of strength training experience were divided into a Cr monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously ingested creatine, and a control group (n = 13) in which they took no supplements. Individuals in the CrM group averaged regular daily consumption of 5 to 20g for 0.25 to 5.6 years. Venous blood analysis for serum albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine produced no significant differences between groups.

Results: Creatinine clearance was estimated from serum creatinine and was not significantly different between groups. Within the CrM group, correlations between all blood parameters and either daily dosage or duration of supplementation were nonsignificant.

Conclusion: Oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements.

Discussion: Questions about creatine's safety are probably the most frequently brought up by people who don't like (and usually don't understand) supplements. This study by Mayhew and colleagues is a welcome addition to the already growing body of creatine safety research. (1,2,3,4,5,6,7)

Most questions revolve around the effects of creatine supplementation on the liver and kidney. These are the two organs are involved in "processing" creatine once it is ingested. The Liver breaks it down and the kidneys excrete it. >From this study, and others before it, we see that long term supplementation with creatine in doses usually taken by bodybuilders (5-20 grams) for extended periods of time do not lead to dysfunction of either organ, nor does it cause abnormalities in the indicators of liver and kidney function.

Considering that fact that creatine supplementation has been shown to enhance anaerobic exercise performance by increasing power output (8), muscular strength and work (9,10,11), and muscle fiber size (12), and to top it off, completely safe even with long term supplementation, its no wonder this is one of my first tier recommendation for effective and safe supplements for putting on muscle size.

 

[B.A.]

Creatine: A Review of Efficacy and Safety


from Journal of the American Pharmaceutical Association
Angie S. Graham, Randy C. Hatton




Abstract
Objective: To provide an overview of the data on the efficacy and safety of the nutritional supplement creatine.
Data Sources: Human studies in English in MEDLINE, Current Contents, BIOSIS, Science Citation Index, and the popular media (including a LEXIS-NEXIS search and information from the World Wide Web and lay media) for 1966 to July 1999 using the search terms creatine, creatine supplement#, creatine monophosphate, and creatine NOT kinase.
Data Synthesis: Creatine use is common among professional athletes. Its use has spread to college athletes, recreational athletes, and even children. Most creatine supplement regimens include a loading dose of 20 to 30 grams divided in 4 equal doses for 5 to 7 days, followed by a 2 gram per day maintenance dose. The increased creatine in the muscle may allow larger stores of phosphocreatine to build, and provide extra energy in the form of adenosine triphosphate. Despite the many clinical trials, high-quality research is lacking. Laboratory investigations of endurance isotonic exercises, strength and endurance during isotonic exercises, isokinetic torque, isometric force, and ergometer performance have yielded roughly an equal number of published studies showing a positive effect or lack of effect. Field studies (i.e., on subjects participating in sports activities) are less impressive than laboratory studies. Performance was more often improved for short-duration, high-intensity activities. Reports have linked creatine to weight gain, cramping, dehydration, diarrhea, and dizziness. Creatine may decrease renal function, but only two case reports of this effect have been published. Creatine appears to be well tolerated in short-term trials.
Conclusion: While creatine may enhance the performance of high-intensity, short-duration exercise, it is not useful in endurance sports. Because commercially marketed creatine products do not meet the same quality control standards of pharmaceuticals, there is always a concern of impurities or doses higher or lower than those on the labeling. Consumers should balance the quality of information supporting the use of creatine with the known and theoretical risks of using the product, including possible renal dysfunction.

Introduction
Creatine use is common among professional athletes, for whom even minute differences in performance can mean the difference between winning and losing. They turn to this amino acid compound with hopes of improving muscle mass, strength, and recovery time. Mark McGwire, Sammy Sosa, and others have openly acknowledged their use of creatine supplements.[1] The Los Angeles Lakers are reported to keep tubs of creatine in their locker room. It has been estimated that 50% of National Football League players, and at least 25% of professional hockey, baseball, and basketball players take creatine. Many college coaches and trainers have been quick to follow the lead of the professionals, and there is concern that high school students and children may use creatine in an attempt to emulate their sports heros.[2] Because creatine is considered a nutritional supplement, as defined by the Dietary Supplement and Health Education Act (DSHEA) of 1994, it is available over-the-counter in pharmacies, health food stores, and supermarkets.
Some coaches forbid or advise against creatine use because its long-term safety profile is unknown.[2] The athletics director for the University of South Carolina has prohibited creatine use without a prescription.[3] Although the International Olympic Committee regulations state that consuming a substance in abnormal quantities for the purpose of artificially and unfairly enhancing performance is "doping," Olympic athletes are permitted to use creatine because of its classification as a nutritional supplement. While it could be argued that creatine should be banned from professional sports, no reliable method currently exists to test for creatine if such a rule is made.

In 1996 creatine sales were estimated at $50 million. Sales exceeded $100 million in 1997, and for 1998 total sales were expected to exceed $200 million.[2] In 1996 the American public purchased 1.2 million kilograms of creatine. By 1998 consumption had risen to nearly 4 million kilograms.[4] With popular magazines running articles with titles such as "The Rise of Creatine, Nature's Steroid," "Packaged Pep," and "Eat Powder: Build Muscle: Burn Calories,"[5-7] and personal endorsements from stars like the Baltimore Orioles' Brady Anderson and Denver Broncos' John Elway,[1] interest in creatine is unlikely to wane. Every day, more people are considering creatine for its purported benefits, and many will turn to their community pharmacist for advice.

This article summarizes the available literature on the efficacy and safety of creatine.

Data Sources and Selection
Data were gathered from the current clinical literature, including MEDLINE, Current Contents, BIOSIS, and Science Citation Index. Multiple literature searches were performed in databases between 1966 and July 1999 using the search terms creatine, creatine supplement# (truncated to capture the key words "supplement," "supplements," "supplementation"), creatine monophosphate, and creatine NOT kinase. Citations were limited to human studies and the English language. Hand searching the reference lists of articles identified additional studies. A magazine and lay journal database available through Melvyl, the database platform of the University of California at San Francisco library, was also searched using the key word creatine. The World Wide Web was searched using LEXIS-NEXIS and by entering the key word creatine into a metasearch engine, scanning the results, and omitting any pages devoted strictly to advertising and sales.

Proposed Mechanism
Creatine occurs naturally in foods, mostly in meat, fish, and other animal products. A typical diet includes 1 to 2 grams of creatine daily. Vegetarians consume much less creatine. Endogenous creatine is synthesized from arginine, glycine, and methionine in the liver, pancreas, and kidney. It is then actively transported from the plasma into skeletal muscle, the location of 95% of the body's total creatine content. Until creatine is broken down to creatinine, it is in dynamic equilibrium in the muscle as either creatine or phosphocreatine, according to the following equation:
Phosphocreatine + ADP (adenosine diphosphate) creatine + ATP (adenosine triphosphate)

In a 70 kg man, approximately 2 grams of creatine are converted to creatinine and excreted every 24 hours.[8,9] Most creatine regimens involve intake of 20 to 30 grams divided into 4 equal doses each day, for 5 to 7 days, followed by a maintenance dose of 2 grams per day divided into 4 doses.[10] Supplementation regimens aim to increase the total creatine transported into muscle tissues. Researchers have shown that supplementation can increase total muscle creatine content by 10% to 20%, with 20% to 40% in the form of phosphocreatine.[11]

In resting muscle, aerobic respiration produces ATP, which is used not only to meet basal energy requirements but also to donate a phosphate group to creatine and replenish phosphocreatine stores. During brief periods of high-intensity exercise, ATP demand may increase to several hundred times the amount used at rest. Phosphocreatine acts as an immediate source of phosphate groups to rephosphorylate ADP to ATP. When phosphocreatine stores run low, performance deteriorates rapidly because the ATP supply is insufficient to meet demand, and aerobic metabolic pathways take over. It has been estimated that both ATP and phosphocreatine stores are depleted after about 10 seconds. By increasing the amount of total creatine in the muscle, creatine supplements raise phosphocreatine levels. Increased phosphocreatine increases ATP levels and extends the duration of high-intensity exercise.[9] Therefore, creatine is considered an ergogenic aid, defined as a "means to enhance energy utilization, including energy production, control, and efficiency."[12]

 

[B.A.]

Clinical Trials
The ability of creatine supplementation to increase strength and improve athletic performance was first suggested by a study in which patients received 1.5 grams of creatine daily for 1 year.[13] Seven patients with gyrate atrophy of the choroid and retina received creatine supplementation to slow the progression of their disease. Patients experienced a 10% weight gain early in their treatment, and some patients reported increased strength. One patient who was an active runner improved his 100-meter sprint time by more than 10%, from 17 to 15 seconds.
Since the publication of the above study in 1981, dozens of clinical trials have examined the effects of creatine supplementation on exercise performance; however, small sample sizes and poor study designs have limited this research, and results are inconsistent. Trials have enrolled between 6 and 36 subjects, have used differing dosage regimens, and have involved both athletes and untrained individuals. Even though one can speculate that increased availability of ATP would dramatically enhance the performance of trained athletes, results have varied in this group, as well. Because of the small sample sizes enrolled, response differences generally must be of a large magnitude to achieve statistical significance; however, a number of studies have shown that, regardless of the characteristics of the subjects or the type of exercise performed, creatine supplementation provides no positive benefit.[14-42] Creatine supplementation studies have involved many types of exercise, including isotonic strength and endurance; isokinetic torque; isometric force; arm, cycle, and kayak ergometer performance; high-intensity prolonged exercise; and endurance tasks at lower intensity. In many cases, exercise tasks that can be measured and quantified in the laboratory setting do not encompass the full spectrum of motion and muscle used in an actual sports activity. Therefore, a positive effect in a laboratory test may not be predictive of improved performance in a sporting event.

Eight trials measured the effect of creatine supplementation on strength and endurance during isotonic exercise, described as muscle contraction against a constant load (see Table 1).[14-17,43-46] Most of these studies involved bench press measurements or other weight lifting activities performed by college athletes. In five of the studies, creatine supplementation was associated with improved performance,[14,43-46] but in three studies no statistically significant change was observed.[15-17]

Five trials measured isokinetic torque and also produced variable results.[15,18,19,45,47] Torque is the turning effect produced when force is applied to a rotational axis; an isokinetic measurement of torque causes the attached muscles to change length at a programmable, constant speed (e.g., arm or leg curls using Nautilus equipment). Isokinetic torque production was increased relative to placebo in three of the studies.[18,45,47] A fourth study involving 20 female athletes found a statistically significant improvement in isokinetic torque during the 10 weeks of maintenance supplementation with 5 grams/day, although no improvement was noted during the initial 4 days of supplementation with 20 grams/day.[19] In the fifth study, also using female athletes as subjects, no improvement was observed following creatine use.[15] The trials are summarized in Table 1.

Four studies examined the effect of creatine supplementation on isometric force (Table 1).[18,20,48,49] Isometric exercises maintain muscle contraction, so that contraction produces increased tension at a constant overall muscle fiber length. An isometric contraction occurs when a muscle develops tension but its fibers never shorten, such as when one pushes against a wall or other immovable object. The four studies of isometric exercise measured grip strength, ankle extensions, voluntary contractions, and static quadriceps force production. Improved performance was observed in three studies.[20,48,49] The results are difficult to interpret, because the largest study involved only 10 subjects[49] and because exercise activities seldom consist of isometric contractions alone.

Several studies have used arm, cycle, or kayak ergometer performance to measure the effects of creative supplementation on exercise performance (Table 2).[16,21-31,44,50-57] In most of these trials, subjects cycled on a bicycle ergometer. Study designs varied widely, with seven trials using athletes as subjects[16,23,25,27,31,44,56] and the rest using healthy adults. Out of 22 studies of creatine's effects on muscular power, 13 showed a statistically significant positive effect following supplementation,[16,21-23,44,50-57] 8 found no effect,[21,24-30] and 1 produced equivocal results, with 1 group from the crossover study showing benefits and the other demonstrating no change.[31] The results are summarized in Table 2.

Research has extended beyond the controlled setting of the laboratory to field studies of actual athletic performance. A summary is provided in Table 3. Of six studies assessing the effect of creatine on high-intensity, short-duration sports such as sprint running and swimming,[14,17,25,32,33,58] only one demonstrated a treatment effect.[58]

Creatine has also been studied in prolonged high-intensity exercise, such as treadmill running or cycling to exhaustion (Table 3). Of eight placebo-controlled laboratory studies,[20,22,34,35,55,59-61] four resulted in performance improvement in subjects using creatine.[55,59-61] In field tests, positive response was noted in only one[62] of six trials.[23,25,32,36,37,62]

Eleven studies have investigated the effects of creatine on endurance tasks (see Table 4), involving prolonged aerobic exercise, such as distance running or cycling. None of the six laboratory-based trials found a statistically significant improvement in performance.[24,27,38-41] A statistically significant positive difference between the placebo and treatment groups was observed in two[58,62] of the five field trials.[36,38,42,58,62] These results suggest that creatine supplementation is unlikely to improve performance of endurance sports.

In summary, creatine supplementation does appear to increase creatine levels in muscle tissue.[11] Higher creatine levels in muscle tissue should correlate with improved performance of short-duration, high-intensity tasks that are likely to use the ATP-phosphocreatine system as a primary source of energy. Positive results, however, have been difficult to attain and consistently replicate, especially outside the laboratory setting. Some researchers have observed that only those subjects whose baseline creatine concentrations were at the lower end of the normal range benefited from supplementation.[63] This may account for the variable results seen in clinical studies. Some variation in results may also be attributed to a "placebo effect," which is well known to be easily induced in athletic events and not noted in any of these studies. Without further, more careful research, the reasons for the discrepancies in trial results will remain unclear.

Adverse Effects
Anecdotal reports have linked creatine supplementation with cramping, dehydration, diarrhea, and dizziness.[2] The Food and Drug Administration (FDA) has warned consumers to consult a physician before beginning creatine supplementation.[10] The Association of Professional Team Physicians has cautioned that creatine may cause dehydration and heat-related illnesses, reduced blood volume, and electrolyte imbalances,[64] and some athletes drink large quantities of water hoping to avoid such effects.[2] Creatine is known to be osmotically active, so that higher intracellular creatine levels may redistribute body water from extracellular fluids or from the general circulation into muscle cells.[46] Judgingfrom the short-term clinical trials performed to date, however, creatine appears to be well tolerated.

No adverse effects were noted in clinical trials, although many trials reported increased body mass in the subjects receiving supplementation. 9,11,12,14,16,21,30,38,40,43,44,46,48,50
,51,54,57,63 It was previously hypothesized that weight gain observed in subjects using creatine might result from an increased rate of contractile protein synthesis,[12] but most researchers now agree that the additional body weight results from water retention. Hultman and colleagues[65] reported significant reductions in urinary output in the initial stages of creatine supplementation. Other researchers have reported increases in skeletal muscle volume, total body water, and intracellular fluid volume after a few days of supplementation. The weight gain observed ranged from 0.7 to 2.0 kg following 5 to 14 days of supplementation.[10] This much weight gain may hinder athletes engaged in endurance sports.

 

[B.A.]

Creatine is broken down and excreted by the kidney as creatinine. Creatine supplementation has been shown to increase 24-hour creatine, creatinine, and urate concentrations.[66] At least one study has found that creatine supplementation increased serum creatinine levels significantly, although levels remained between 1 and 1.5 mg/dL, a normal range for people undergoing intense physical training.[11] The lack of any adverse renal effects in clinical trials to date suggests that subjects with normally functioning kidneys can eliminate the increased creatinine load that results from creatine supplementation; however, some experts have warned that long-term creatine use could decrease kidney function, and recent case reports[67,68] suggest that not all patients are able to sufficiently process excess creatinine.

The April 25, 1998, issue of the Lancet[67] reported a case of renal dysfunction following creatine use. The patient was a 25-year-old man receiving cyclosporine for steroid-resistant focal segmental glomerulosclerosis. Although his cyclosporine levels had been stabilized within the therapeutic range, his renal function declined between appointments in June 1997 and mid-October 1997. Between the two dates, serum creatinine concentrations increased from 1.2 mg/dL to 1.8 mg/dL, with a corresponding decrease in creatinine clearance from 93 mL/minute to 61 mL/minute. The patient denied use of nephrotoxic medications, but reported initiating creatine supplementation with a loading dose of 5 grams 3 times per day for 1 week, and a maintenance dose of 2 grams per day. Renal function returned to baseline 1 month after creatine supplementation was discontinued.

A second case report[68] describes interstitial nephritis in a previously healthy 20-year-old man using creatine. The patient had begun using 5 grams of creatine 4 times per day approximately 4 weeks prior to the onset of symptoms. He presented to the hospital with a 4-day history of nausea, vomiting, and bilateral flank pain, and was found during physical exam to be dehydrated and experiencing diffuse abdominal tenderness. Laboratory studies revealed a serum creatinine level of 1.4 mg/dL, and 4+ protein and 1+ blood in the urine. While the patient was hospitalized and treated with pain medications and intravenous fluids, his blood pressure rose from 140/90 to 160/100 mm Hg, his serum creatinine reached a peak of 2.3 mg/dL, and his urinary protein excretion was 472 mg per day. Renal biopsy demonstrated acute focal interstitial nephritis and focal tubular injury. The patient's laboratory values and symptoms eventually normalized.

The studies included in this review reported no serious adverse effects, but few included a mechanism for formally assessing adverse effects, and they all involved short-term administration to young, healthy volunteers. It is not known what effects may be produced in other patient populations. Derek Bell from the Houston Astros was hospitalized twice in 1998 for renal dysfunction, and has publicly blamed creatine for his ailments.[1] It cannot be stated unequivocally that creatine is harmful to the kidney, but until the relationship is clarified it would be prudent to avoid creatine supplementation in all patients with impaired renal function and to advise patients to seek medical attention immediately if they experience flank pain, hematuria, nausea, or vomiting while using creatine.

There are no controlled toxicology studies using the doses recommended to enhance athletic performance. In fact, although most creatine manufacturers recommend loading with 20 to 30 grams per day for 5 to 7 days and then cutting back to a maintenance dose of 2 grams per day, some athletes choose to "mega-dose" creatine. Brady Anderson of the Orioles told reporters that he uses 10 times the recommended dose.[1] Yet, even the maintenance dose recommended by manufacturers has not been proven safe for long-term use.

All nutritional supplements carry a risk of contamination with impurities, because their manufacturers are not bound by the same manufacturing practices that FDA requires for drugs. The high doses recommended for creatine supplementation, and the even higher doses used by some individuals, could increase exposure to a toxic impurity.[8] Contamination, like that reported with tryptophan and 5-hydroxytryptophan, is possible. Unsubstantiated reports on the Internet claim that some creatine products are contaminated with dicyandiamide and dihydrotriazine, which have unknown effects,[69] and others claim that some creatine powders are mixed with baking soda, or certain impurities such as rat hairs.[2] Studies should investigate whether contamination causes adverse effects.

Conclusion
Although many trials have studied the effects of creatine, high-quality research is lacking. Studies have employed very small sample sizes and produced variable results. Furthermore, the results observed in highly trained athletes cannot necessarily be extrapolated to the general public. It is also not clear whether individual variations in baseline creatine levels affect the efficacy of supplementation. Little information exists on the short-term or long-term safety of creatine. Drug interactions with most supplements, including creatine, have not been studied.
Commercially marketed creatine supplements do not meet the same rigid quality control standards as pharmaceuticals, because they follow looser DSHEA rules. Therefore, it is difficult to apply efficacy and safety results from published trials to general practice. The dose delivered by a commercially available product may be more or less than that suggested by the labeling. This could influence the effectiveness of creatine. The lack of adequate quality control could result in impurities in creatine supplements, which could lead to unexpected adverse effects.

Although creatine is becoming increasingly popular, the evidence of its benefits is limited at best. Large-scale, well-controlled studies must show the positive effects of creatine supplementation before pharmacists can recommend it. Patients should understand that based on its mechanism of action, creatine may possibly enhance their performance of high-intensity, short-duration (i.e., < 60 seconds) exercise such as sprinting or power-lifting, but that benefits have not been proven in the clinical trials to date. Patients engaged in endurance sports should know that there are few data supporting creatine use for lower-intensity, longer-duration exercises, and that the weight gain associated with creatine supplementation may be detrimental to their performance. Pharmacists should advise patients to consult with their physician before beginning creatine supplementation, and to immediately report adverse effects, such as nausea, vomiting, dizziness, or flank pain. Because of the potential risks and the questionable benefits, pharmacists should warn patients with renal dysfunction to avoid creatine supplements. If consumers choose to use creatine supplements, they should be counseled on the variable efficacy data and the unknown risks of toxicity.

The authors declare no conflicts of interest or financial interests in any product or service mentioned in the manuscript, including grants, employment, gifts, and honoraria.

 

[waldo]

Very interesting, thanks for that

Personally took creatine last summer, found it made a very big difference. Only realised how big just recently when looking at photo's from last summer vs now.