Ultimate Creatine Handbook (Seriously)

This is a series of articles from our board, which I encourage you guys to check out, and this truly is the ultimate creatine guide. If you have a question after reading all of this, it doesnt exist. This is extensive (long) but useful. I dont know about you guys, but Im tired as hell of seeing creatine questions, they're not too bad here (thank god) and since this is my second home, Id like to share this massive handbook with you guys




From Layne Norton

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.

From Sheesh at AnabolicMinds

I did a search for 'creatine' using the search function on the forum and went over most of the threads that were found (A search for 'creatine' yields 4,376 results). After reading most of the threads I assembled the following FAQ, covering questions that weren't answered by Layne in his article.



Creatine FAQ by Icex999



"I know that creatine with dextrose is good as a part of an after workout shake, but how about on rest days when you are just trying to keep the creatine level up in the blood. Ya still have to mix it with dextrose or whatever? Seems like some unnessesary calories if ya don't need it." - gbat


Yes, you're right it is indeed unneccesary calories. As a general rule of thumb, creatine should only be mixed with dextrose post-workout. Insulin is one of the most anabolic hormones produced by the body, but it is also one of the most fattening hormones produced by the body. After a workout, the insulin spike drives more creatine into the muscles and most of the sugar (dextrose in this case) is shunted towards muscle + liver glycogen resynthesis. However, when not taken post-workout, all that extra sugar will probably end up in your adipose cells, unless you're in a fasted state. So to sum things up, on rest days, just take creatine by itself



"I am a creatine non responder. I heard that swole and V12 might work. Be4 I try one, has any non responder of regular creatine powder tried swole or V12? Which did you try and did you respond to it?" - asianlifter


Although the jury is still out on which of these products is the best of the two, so far lots of positive feedback has been coming in on both products. Many creatine non-responders say that these products worked great for them, so either one is recommended. A recent article in Flex magazine stated that this may be because of the glycocyamine content of each of these products. If you can find glycocyamine by itself, adding 3 grams of it to 5 grams of a plain, micronized creatine would actually be the best thing to do.



"I have been takin creatine for about 2 months now and have seen great gains in both stregth and also musclemass...When i stop this cycle in about a week, will i start to lose eitha the muscle or the stregth..I heard there has been debate about this. My friend says as soon as i go off it the water will be released and i will lose mass and stregth......" -
|||Bonez|||


Although this topic hasn't been researched yet, here is the general agreement between those 'in the know'. Your strength will decrease, but nothing to worry about. You will still probably be able to lift heavier weights that what you were lifting when you started creatine. You will also lose a little bit of size, all of it water retention, nothing significant enough to be worried about it.



"I dont have any grape juice, is it ok to load it with water?" -dixie945466


Yes, it's fine to take creatine with water. Actually, as stated in the first question, I believe that the only time you should take creatine with sugar is post-workout.



"Is it possible to sniff creatine and get the same effects as drinking it? just wondering. im not really thinking of doing but im curious." - tre14


Yes, you COULD snort creatine, but the effects wouldn't be the same as drinking it. Most particles of creatine dust are just too big to make it through the nasal cavity into the blood stream. Even micronized creatine might be too large. This subject has never been researched, and I doubt it ever will be so I can't give you a solid answer. All I can say is, if you decide to snort it, it's a stupid idea, but best of luck! Keep 911 on speed dial just in case you congested to the point of suffocation....



"If dextrose is like table sugar then would it be ok to take my creating in my coffee?"
-WanaKnowMore


Dextrose isn't like table sugar. Dextrose has higher glycemic index than table sugar, which means it spikes your blood sugar faster and higher which in turn leads to more insulin being released, which will drive the creatine into your muscles. The coffee leads us to our next question....



"Will consuming caffeine while on creatine affect my results?"


The answer to this one is yes and no. Recent research on the topic has shown that caffeine affects the performance enhancing benefits of creatine. Therefore if you're taking creatine to get stronger or faster, then limit your caffeine intake while on creatine. However, consuming caffeine while on creatine does not affect the cell-volumizing aspect of the supplement. So if you're taking it to get bigger, taking it with caffeine is fine.



"Will creatine make my balls shrink/give me gynecomastia (man breasts)?" - Countless
Newbies


No. The only things that do these dastardly deeds are things that act as external sources of testosterone, such as steroids and pro-hormones.



"ok i know that when you are taking creatine you need to drink alot of water but i was wondering that if i was just to drink about a gallon of water at night and only a little during the day would that be the same as spreading 2 gallons out throughout the whole day?"
- brianSP


Taking your water this way wouldn't affect your creatine results at all. However, I'd recommend drinking the water throughout the day as a constant water consumption throughout the day provides optimal hydration.


"Is german creatine superior to non-german creatine?"


Yes, but this is mainly because german creatine is micronized. Any kind of micronized creatine would do just fine.




"Which supplements brands use german creatine?" -Thi@go.


Anything that is labelled as creapure contains German creatine. Some companies may also state that their creatine is german, which is an obvious giveaway.



"How long is it ok for creatine to be in water?" - TranceNRG


If the water is pure (ph=7) and 4 degrees C, then 30 days. In pure water at 25 degrees C, 3 days. Even at a water pH of 3.5, it is 97.5% stable after 3 hours. (Answer courtesy of K(same))



Does anyone know how long you can be off of creatine without having to do another loading phase? -coconut


1-2 weeks.



"I want to take creatine, but I have heard that once you start taking creating for an extended period of time that your body doesn't produce its own creatine after a while and your weak during that period. Is this true or can I start loading?" - BigBryan1


Your body will continue to produce its own creatine. Go ahead and start your creatine.



"Ok, I have read articles that advocate taking Creatine with juice, and some articles that Juice works against the Creatine.

So the question is, is either side correct, or is it even known how to take the Creatine?"
-CMM


The side that advocated taking creatine with juice is right (grape is best). Although this isn't the best way to take creatine, it won't 'work against the creatine'.



"I've started taking it for the first time. It's not easy to take though. It makes me feel sick and 15 minutes after taking it I shit like an elephant. Is this normal? I am taking doses of 15-30g as recommended by the manufacturer as a loading phase." -itch


It is not normal to have to have gastrointestinal problems with creatine. Your stomach obviously isn't agreeing with such a huge dose of creatine. The loading phase isn't even necessary, so just drop down to a 'maintenance level' of 3-5 grams of creatine per day.



"Well, I just started bulking about 14 weeks ago and I've gained about 25 lbs with the help of creatine. Though I'd like to gain more, I'm starting to outgrow my pants, so I've decided to start cutting.

Should continue taking creatine? " - Gravity


Taking creatine while cutting is fine, and I'd actually reccommend it if you saw positive results from it while bulking.

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.



Additional References:


1: Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol. 1997;76(6):566-7.

2: Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999 Aug;31(8):1108-10.

3: Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH. American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc. 2000 Mar;32(3):706-17.

4: Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med. 2000 Aug;34(4):284-8.

5: Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med. 2000 Sep;30(3):155-70.

6: Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M, Coglianese R, Smith L, O'Bryant HS, Fry AC, Starks M, Keith R, Stone ME. Creatine supplementation and health variables: a retrospective study. Med Sci Sports Exerc. 2001 Feb;33(2):183-8.

7: Benzi G, Ceci A. Creatine as nutritional supplementation and medicinal product. J Sports Med Phys Fitness. 2001 Mar;41(1):1-10.

8: Earnest CP, Snell PG, Rodriguez R, Almada AL and Mitchell TL (1995) The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 153: 207-209

9: Casey A, Constantin-Teodosiu D, Howell S, Hultman E and Greenhaff PL (1996) Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 271: E31-E37

10: Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L and Hespel P (1997) Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 83: 2055-2063

11: Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ and Kraemer WJ (1999) Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 31: 1147-1156

12: Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ and Kraemer WJ (1999) Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 31: 1147-1156

Using Creatine While "On"


All anabolic steriods are synthetic compounds whose structure is similar to that of the natural male sex horomone
testosterone. Testosterone affects development of the male body in two important ways: it has an anabolic effect-increased growth, expecially of muscular and skeletal tissue and an androgenic effect-increased development of mail sexual characteristics. Once taken into the bloodstream, anabolic steriods bind to hormone receptonrs on skeletal muscle and other cells and stimulate synthesis of certain specific enzymes. These enzymes promote two improtant biochemical reactions: creatine phoshate systesis and protein sythesis. Creatine phospate is a molecule that can be metabolized in the absense of sufficient oxygen as a shot-term source of energy. Increased creatine phospate synthesis thus allows athletes to train harders and for longer periods of time, and therefore build more muscle. Protien synthesis is essential for long-term development of increased muscle mass or "bulk". In addtion, anabolic steriods promote nitrogen retention by the body. By allowing for better utization of the nitrogen in ingested protein, anabolic steriods help athlets to build mass. However this effect is offset by the bodys homeostatic mechanisms, which are designed to maintain a stable environment: therefore in order to increase body mas by using anabolic steriods, athletes must also adhere to a diet with suffiecent protein and calories - up to 10,000 calories daily with 300 to 400 grams of protein.



Question: Creatine synthesis, if you increase creatine intake while on AS will it help you get stronger. I had always thought it just added to the amount of water you retain ?


Although creatine does have testosterone-like effects,it doesn't act as a steroid hormone.Instead,it's a mediator of some of the
androgens' anabolic effects.In fact,steroid users get far more out
of their cycles if they take in massive amounts of creatine along
with the drugs.Androgens are among the hormones that can force the entry of creatine into muscle cells.While there's a clear
relationship between muscle strength gains and increases in muscle creatine stores,unfortunately,the relationship is not as obvious when it comes to increases in muscle mass.Animal-based studies have shown that the muscles of untrained rats take up as much creatine as the muscles of trained rats,but the ANABOLIC effects of creatine are only obvious in trained rats.Therefore,training increases the muscles sensitivity to the anabolic actions of creatine.(Although it's not related to this article,the study also demonstrated that the anabolic effects of creatine are DIRECT,and not mediated by waterretention.In fact,in the 1970s American and Russian studies pointed out a DIRECT anabolic effect of creatine on muscle cells.)Testosterone increases the muscles'sensitivity to the anabolic properties of creatine in addition to enhancing the creatine buildup in muscle fibers.It's also obvious that part of the strength gains people experience while on steroids are mediated by an increase in muscle creatine stores.An interesting discovery A/S users have made is that they should dramatically increase their creatine intake during a cycle to boost the potency of the steroids.Thanks to creatine,people can build more muscle mass with fewer drugs.Anecdotal evidence from A/S users points out that it
takes at least 10-15 grams(maintenance)of creatine a day to visibly enhance the the anabolic potency of a steroid stack.There are probably good reasons for the increased creatine requirement when androgen levels are high.As mentioned above,steroids increase the muscle uptake of creatine,and if the muscles are ready to accept more creatine,why not give it to them?I also think that even though steroids enhance creatine synthesis,they may increase creatine degradation as well-so more creatine is used up every day.That could be due to an increase in muscle creatine turnover and also the fact
that an elevated muscle protein synthesis rate will likely consume
creatine at a faster rate.Other reasons for a higher creatine
requirement may be indirect.Because the muscles of drug users are stronger and receive more training,they may waste greater amounts of creatine during training.Once inside the muscle,creatine provides not only an anabolic effect,but also a rapidly mobilized source of fuel.Muscle protein synthesis is a process that wastes great amounts of energy.Anabolism is an ATP-dependent process,which means that it's essential for protein synthesis.If the cellular level of ATP is reduced even a little,IT STOPS ANABOLISM.So even if you can increase the testosterone content of your muscles,nothing will happen if your
ATP level is low.Creatine supports anabolism by providing energy to the muscle...

Creatine May Protect Against Brain Damage

By Elaine Zablocki
Reviewed By Dr. Jacqueline Brooks


Nov. 2, 2000 -- The dietary supplement creatine is widely used by athletes to increase muscle mass and performance. Now a new study, conducted in animals, suggests that it may also protect against damage due to brain injury in people.


"Professional quarterbacks in the NFL sustain many concussions, with less damage than we might expect," senior author Stephen W. Scheff, PhD, tells us. "That could be because they're taking creatine." Scheff is professor of anatomy and neurobiology at the University of Kentucky School of Medicine and associate director of basic research at the Sanders-Brown Center on Aging, both in Lexington.


In this study, published in the November issue of The Annals of Neurology, researchers fed rats and mice a diet high in creatine, and then simulated a concussion. They found that rats who ate a creatine diet for four weeks had a 50% reduction in brain damage, compared to rats on a normal diet. Mice who received three days of creatine pretreatment had a 21% decline in damaged cells, while those who received five days of creatine pretreatment had a 36% decline.


This doesn't mean you should eat creatine ahead of time before having a concussion, because concussions obviously aren't planned. But because these animal studies show creatine works by increasing energy production in the part of the brain cells responsible for generating the body's energy, called the mitochondria, it may be possible to find a substance that has a similar effect if taken soon after a concussion or brain injury. Scheff and other researchers have looked at several substances and are now conducting tests on one promising possibility.


Just as important, creatine may be valuable in several diseases where mitochondrial dysfunction plays a role. According to Sinclair Smith, ScD, many previous studies have indicated that creatine has the capacity to protect nerves. These reports have shown that it has good results in Lou Gehrig's disease (also known as amyotrophic lateral sclerosis, or ALS) and multiple sclerosis among others, he tells us. Smith is an assistant professor of physiology in the occupational therapy department at Temple University School of Medicine in Philadelphia.


He believes creatine could potentially assist in treatment of diseases involving nerves and muscle. "I don't expect it will be a cure, but it may slow the disease process. Future research needs to focus on how creatine works in humans, and how it works in conjunction with other treatments. This is a hot area right now."


Head injuries predispose people to early onset of Alzheimer's disease, though no one knows why. This suggests creatine might also possibly slow Alzheimer's progression, Scheff speculates. "We don't know if it will stave off the disease, but it might be worth investigating."


However, since creatine is a nutritional supplement, it isn't regulated by the FDA, and it hasn't been tested for safety in human beings. At the same time, lots of athletes are taking it, and lots of health food stores are selling it.


Last May, the Blue Cross and Blue Shield Association released a statement warning about potential negative consequences of creatine. Although there have been no formal studies, observers say it may be linked to cramps, diarrhea, nausea, dizziness, high blood pressure, and liver and kidney problems.


But Scheff says creatine is an inexpensive substance with no known side effects. "Three grams of creatine per day is a maintenance dose," he says. "I buy it at the local grocery store before I go skiing."


Edward J. Kasarskis, MD, PhD, agrees creatine may play a valuable role in fighting diseases of the nervous system. When mice with ALS are fed creatine, they live longer, he tells us. Now studies are planned to test creatine in humans with ALS. Meanwhile, since creatine is readily available, many of these patients are already taking it on their own.


"When people are faced with a desperate disease that has no effective treatment, they don't worry about side effects. They're eager to try something that may prolong life. We don't encourage them; we don't discourage them. Is creatine safe and effective for this condition? We don't know," says Kasarskis, a professor of neurology at the University of Kentucky's Chandler Medical Center and a member of the Amyotrophic Lateral Sclerosis Association's Subcommittee on Gulf War Veterans and Amyotrophic Lateral Sclerosis.

Effects of creatine on Lipolysis


J Appl Physiol 2002 Aug 16; [epub ahead of print]

Creatine supplementation influences substrate utilization at rest.

Huso ME, Hampl JS, Johnston CS, Swan PD.

Department of Nutrition, Arizona State University, Mesa, AZ, USA.

The influence of creatine supplementation on substrate utilization during rest was investigated using a double-blind crossover design. Ten active men participated in 12 weeks of weight training and were given creatine and placebo (20 g/d for 4 d, then 2 g/d for 17 d) in two trials separated by a 4-week washout. Body composition, substrate utilization, and strength were assessed following week 2, 5, 9 and 12. Maximal isometric contraction (1-RM) leg press increased significantly (P < 0.05) following both treatments but 1-RM bench press was increased (33 kg +/- 8, P < 0.05) only following creatine. Total body mass increased (1.6 kg +/- 0.5, P < 0.05) after creatine but not after placebo. Significant (P < 0.05) increases in fat-free mass were found following both creatine (1.9 kg +/- 0.8) and placebo (2.2 kg +/- 0.7) supplementation. Fat mass did not change significantly with creatine, but decreased after the placebo trial (-2.4 kg +/- 0.8, P < 0.05). Carbohydrate oxidation was increased by creatine (8.9% +/- 4.0, P < 0.05), while there was a trend for increased RER after creatine supplementation (0.03 +/- 0.01, P = 0.07). Changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine following weight training.


Note: RER, or Respiratory Exchange Ratio, is a measure of how much fat vs. how much glucose is being used for fuel. The higher the RER, the more glucose/less fat there is being burned.

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.

Creatine and Alcohol From MuscleChem

II. CREATINE AND ALCOHOL MIX

Background
Although no published studies have specifically examined the effects of alcohol on the effectiveness of creatine, alcohol does have known effects on muscle metabolism and survival. These indirect consequences of alcohol might, in turn, influence how well we respond to creatine supplementation.

Fast Twitch Muscle Fibers: Anaerobic
Not all muscles are the same. Muscle fibers can be loosely distinguished on whether they mediate fast or slow movements. Fast muscle fibers, also known as Anaerobic, do not require oxygen to work. Thusly, anaerobic muscle fibers are fast, since they are not limited by oxygen availability. On the other hand, they tire rapidly. Therefore, fast muscle fibers are fast to respond and fast to fatigue.

Fast (Anaerobic) muscle fibers are called into play when we undertake explosive movements. Lifting heavy weights and sprinting are examples of exercises recruiting fast muscle fibers. Did you know that professional sprinters often run the 100-meter race on a single breath? This is because breathing isn't mandatory while using anaerobic muscle fibers! However, because anaerobic fibers also fatigue rapidly, these activities can only be maintained briefly, approximately 10 seconds. In order to recuperate, however, fast muscle fibers do require oxygen. This is why we breathe harder following all out sprints.

Slow Twitch Muscle Fibers: Aerobic
Slow muscle fibers, on the other hand, are Aerobic. Aerobic simply means that slow muscle fibers require oxygen to generate force. As a consequence of their oxygen-dependency, these muscle fibers generate force more slowly. In other words, oxygen availability limits how rapidly slow muscle fibers respond. Therefore, slow muscle fibers provide lower forces, but last much longer. Activities calling into play slow muscle fibers require oxygen, i.e. breathing. Marathon runners rely heavily on slow muscle fibers. Obviously, you wouldn't want to run a marathon while holding your breath.

To summarize, the reason we can only sprint briefly, while we can walk for hours, is that these activities call into action different types of muscle fibers. Sprinting calls into play fast (anaerobic) muscle fibers. Fast muscle fibers generate brief, explosive forces. On the other hand, slow (aerobic) muscle fibers are used for movements lasting more than a few seconds. The amount of force generated by slow muscle fiber is much less and can only be maintained for as long as our breathing allows.

Creatine & Fast Muscle Fibers
Just as not all muscles are the same, creatine doesn't influence all muscle types in the same manner. Creatine preferentially increases the work output of fast muscle fibers. Recall that fast muscle fiber do not require oxygen to generate force. Because of creatine's preference for fast muscle we would notice an increase in sprint performance, while our jogging performance would go mostly unchanged. In other words, we are actually feeding fast muscle fibers by supplementing with creatine!

Protein Synthesis & Muscle Growth
It is natural that some muscle damage occurs during exercise. In fact, this exercise-induced muscle damage is essential for subsequent muscle growth. Simply speaking, we literally breakdown our muscles during exercise and rebuild them during recovery. Whether our muscle mass increases depends on which of these two processes predominates. For example, if muscle breakdown exceeds muscle regrowth, then we lose muscle mass. Protein synthesis, or the production of new muscle proteins, is an essential part of this rebuilding process following exercise.

Alcohol & Muscle Growth
Importantly for today's discussion, it appears that short-term alcohol use inhibits muscular protein synthesis. In fact, this effect is particularly pronounced in fast muscle fibers, especially after prolonged alcohol use. The scenario would be detrimental for any athlete trying to gain muscle mass and strength through training. After all, isn't the goal of training to increase muscle protein synthesis?

The problem is that creatine allows us to work harder, which is generally a good thing. However, this would also mean that muscle recovery is more critical while supplementing with creatine. Now, as alcohol consumption inhibits protein synthesis, a potentially fruitless situation may arise by mixing the two. That is, creatine and alcohol.

Finally, there is also some indication that creatine also stimulates protein synthesis. This effect may underlie part of creatine's benefit. If this is so, then alcohol consumption would offset this benefit of creatine as well.

Note: Keep in mind these important points:
Alcohol inhibits protein synthesis in fast muscle fibers.
Protein synthesis is essential for muscle growth and development.
Protein synthesis is important for muscle recovery.
Creatine increases the work output of fast muscle fibers.
Thus, fast muscle recovery is more critical during supplementation.
Creatine may increase protein synthesis as part of its benefit.
Alcohol may be particularly damaging during creatine supplementation.

CAN CREATINE REDUCE MUSCLE DAMAGE?From MuscleChem

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.

Creatine and Side EffectsFrom MuscleChem


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".

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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

Another Creatine and Fat Loss From MuscleChem


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.

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IV. 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.

Creatine and Injury Recovery From MuscleChem

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.

Creatine and GH From MuscleChem

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