Creatine Benefit and Creatine side effects.
 

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If you are planning to take creatine monohydrate to increase muscle mass and strength, consult your physician if you have medical problems or if you are taking medicines, and please read this creatine information.
        A cautious approach to a creatine supplement would be to limit intake to 3 to 5 grams almost every day for three weeks followed by 3 grams two to four times a week. It would be wise to take a week or so off each month. It would also be wise to take a full month or so off every 3 to 4 months. Of course these creatine guidelines will vary between individuals. The amount and frequency of creatine use depends on how much muscle gain a person wants to maintain. Athletes and large individuals would require higher amounts of creatine, while non-athletes and small individuals would require less. There are a number of other factors that influence the amount of creatine intake including diet, sex, age, concurrent use of other supplement or medicines, medical condition, genetics, etc.
        After the creatine supplement is completely stopped, there is often a gradual decrease in muscle mass over time (days and weeks) probably to the level that it was before creatine intake. The rate of this decrease varies among individuals and also depends on dietary intake of creatine, protein and workout regimen. Taking creatine again generally restores muscle mass rather quickly.
        Creatine supplement use results in increased body weight and total body water content (see study at bottom of page).

What is Creatine?
Creatine is not an herb, mineral, vitamin, hormone, or steroid. Creatine is a natural nutrient found in our bodies and the bodies of most animals. Approximately 95% of the body's creatine supply is found in the skeletal muscles. The remaining 5% of creatine is scattered throughout the rest of the body, with the highest concentrations in the heart, brain and testes.
    The human body gets most of the creatine it needs from food or dietary supplements. Creatine is easily absorbed from the intestinal tract into the bloodstream. When dietary consumption of creatine is inadequate to meet the body's needs, a limited supply can be synthesized from the amino acids arginine, glycine and methionine. This creatine production occurs in the liver, pancreas and kidneys.

Creatine Powder, Source Naturals  
 Creatine Monohydrate, 3 g per teaspoon 

Vegans and Creatine
Vegetarians, particularly those who are on a strict lacto-ovo-vegetarian (LOV) diet do not ingest much creatine since creatine is mostly found in meats, fish, and chicken. Creatine helps muscles stay bulky and strong.
   In a study published in the Journal of Sports Nutrition and Exercise Metabolism, thirty-two healthy men, who regularly consumed an omnivorous diet, were split into two groups. One group consumed a LOV diet while the other group had an omnivorous diet (they ate everything). The study lasted 26 days. In addition to their diet, on day 22 of the study, subjects were assigned in a double-blind manner to receive either creatine monohydrate 0.3 g per kilogram of body weight per day or an equivalent dose of placebo for 5 days. The results demonstrated that consuming a LOV diet for 21 days decreased muscle creatine concentration in individuals who normally consume meat and fish. However, the creatine content of muscle in the LOV group returned back to normal after a period of only 5 days.
   Creatine, 5 g a day for six weeks, has been shown to improve brain performance (memory and intelligence) in adults who are vegetarian.

Creatine Side Effects and Cautions
Nausea, stomach upset, dizziness or weakness, loose stools, diarrhea, and weight gain are the most common creatine side effects, and generally occur with creatine dosages greater than 5 grams a day.  Another creatime side effect sometimes reported is muscle cramping. Strains and sprains can occur (perhaps even muscle tears?) when individuals over enthusiastically and rapidly increase their workout regimen before their tendons and ligaments have adapted to the increase in muscle size and power. 
   Long-term side effects of daily creatine monohydrate ingestion, especially in high dosages, are currently not known.  There is a possibility that excess creatine can put stress on the kidneys and liver.  Creatine converts into creatinine which, in high dosages, could act as a toxin. Whether there is a potential for increasing the risk of cancer with regular high dose use is currently not known. I discourage the regular, high dose use of creatine unless frequent breaks are taken.  Individuals with kidney disease should not use creatine.
   One study shows long term creatine use for 21 months did not influence blood studies (metabolic markers, muscle and liver enzymes, electrolytes, lipid profiles, hematological markers, and lymphocytes). Kreider RB, et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes.   Mol Cell Biochem. 2003 Feb;244(1-2):95-104.
   I have also come across a few anecdotes about high dose creatine causing side effects of anxiety, irritability or depression. Time will tell whether creatine is responsible for these cognitive changes.
   There are no reports to date that creatine influences the size of genital organs or has a significant effect, positive or negative, on sex drive. Creatine doesn't seem to have a direct effect on libido, although feeling good about one's toned body could influence self-image and how others react to us and make us feel more attractive and sexual. The influence of creatine on sperm count or motility, if any, is not known at this time.
   Short term creatine supplementation does not seem to affect blood pressure, heart rate, or kidney function. A small to modest amount of alcohol intake should not interfere with low dose creatine use. I don't advise taking creatine while pregnant. There are no credible reports of hair loss as a creatine side effect.

Creatine Monohydrate and Teenagers
At this point I do not recommend anyone younger than 18 to use creatine except under medical supervision. If your personal physician and parents approve your use of creatine, it should only be taken for a brief period of time, such us a couple of months for a particular sports season, and then you should be off it the rest of the year. Daily dosage is best kept to 3 gm, with two days off per week.
   I am uncomfortable with teenagers using creatine without supervision since they often do not know their limits. My website gets frequent emails from parents wanting to know whether creatine is safe for their teenage son or daughter.
   Since creatine is readily available over the counter, it is unlikely that we can prevent teenagers from using it. Therefore, a "Just Say No" policy won't work. What we can do, though, is have a balanced viewpoint and encourage communication between teenagers, parents, coaches, and a physician.
   I am definitely against teenagers using hormones.

How Does Creatine Work?
Creatine is an essential player in the primary energy source used for muscle contraction. It exists in two different forms within the muscle fiber: as free (chemically-unbound) creatine and as creatine phosphate. This later form of creatine makes up two-thirds of the total creatine supply. When your muscles contract, the initial fuel for this movement is a compound called ATP. ATP provides its energy by releasing one of its phosphate molecules. It then becomes a different compound called ADP. Unfortunately, there is only enough ATP to provide energy for about 10 seconds, so for muscle contraction to continue, more ATP must be produced. Creatine phosphate comes to the rescue by giving up its phosphate molecule to ADP, recreating ATP. This ATP can then be burned again as fuel for more muscle contraction.
        The bottom line is that your ability to regenerate ATP depends on your supply of creatine. More creatine, more ATP remade, and more ability to train your muscles to their maximum potential. It's that simple. This greater ATP synthesis also keeps your body from relying on another energy system called glycolysis, which has lactic acid as a byproduct. This lactic acid creates the burning sensation you feel during intense exercise. If the amount of acid becomes too great, muscle movement stops. But if you keep on using ATP because of all the creatine you have, you can minimize the amount of lactic acid produced and actually exercise longer and harder. This helps you gain strength, power and muscle size; and you won't get fatigued as easily.
        Creatine has also been shown to enhance your body's ability to make proteins, especially the proteins within the muscle fibers. Two of these proteins, actin and myosin, are essential to all muscle contraction. So when you build up your supply of these contractile proteins, you actually increase your muscle's ability to perform physical work. And the more work you do (whether it's lifting weights or running 100-meter dashes), the stronger you become over time. Creatine can also absorb intracellular water, thus resulting in a higher muscle volume. This could lead to the "pumped up" feeling and look. An additional way creatine increases muscle size is thought to be its fluid retention abilities within muscle tissue (see study at bottom of page).

 Is Creatine monohydrate better utilized if taken with other nutrients?
 One study shows co-ingestion of alpha-lipoic acid with creatine and a small amount of sucrose can enhance total creatine content in muscle as compared to the ingestion of creatine and sucrose or creatine alone.

Safety of long term Creatine monohydrate ingestion
To investigate long-term effects of creatine monohydrate supplementation, 18 professional basketball players of the Spanish Basketball League participated in a longitudinal study. The subjects ingested 5 g creatine monohydrate daily during three competition seasons. Blood was collected five times during each of the three official competition seasons (September 1999-June 2000, September 2000-June 2001 and September 2001-June 2002). Standard clinical examination was performed for 16 blood chemistries. Results: blood studies over a 3 year period did not indicate any major abnormalities.
     Dr. Sahelian says: Daily supplementation with 5 grams of creatine monohydrate 8 months of the year appears to be safe. Still, I would prefer taking an additional one week off each month just to be extra safe.

Creatine Monohydrate Emails
Q. I once wrote to Dr. Sahelian about whether creatine monohydrate supplements were natural or synthetic, and I was told that they're actually synthetic. Now I know that creatine itself is a natural nutrient, but honestly I'm trying to take in things with as little processing as possible, and that are as organic as possible. So with that in mind, are there any "natural" forms of creatine supplements? Or, as I suspect may be more likely, are there any foods or nutrients that could have similar energy-enhancing, muscle-building benefits? Things such as Peruvian Maca powder (which apparently many athletes use for strength and muscle building) and Bee pollen, and perhaps Ginseng - Chinese or Siberian - come to mind.... am I correct in these two, and are there others? And finally, should I necessarily be that concerned about the "inorganic" or synthetic/chemical nature of creatine supplements?
     A. Creatine is a natural substance found in most protein foods, however the creatine supplement that we buy is made synthetically. As such, it may not be 100 percent pure. However, I am not overly concerned that the moderate use of creatine, such as 3 mg a few times a week with a week off each month will cause much of a problem. Protein powder is another way to improve muscle mass, but I am not convinced that herbs are a good option.

Q. My question is regarding information read on your website concerning Creatine and behavioral changes. My husband has been taking Creatine for about 1 month now, since he has started taking it several people have noticed increased behavioral changes and one person even said "it is like his whole personality has changed" There are also several other things going on in his life that could be the cause of depression, but I am afraid that the Creatine could be compounding the problems.

Q. Thanks for sharing your research on Creatine monohydrate.   Up until the point I discovered your site; I had been taking 5 mg of Creatine each day for about 5 weeks.  Creatine provided just the boost I needed for my workouts but unfortunately, now I realize that it also made me depressed.  I have a history of depression and have been in therapy for a few years now.  I have been free of any extended episodes of depression, lasting more then a couple days, for the past 2 years.  I began to notice a change in my mood about 2 weeks after starting the Creatine.  I felt tired, cranky and a definite lack of enthusiasm for things I normally enjoyed.  I began looking for things going on in my life that could be causing this change but realized that the only thing that had changed recently was the addition of Creatine to my supplement routine.  This got me on the internet where I found your site.  I quit taking Creatine 1 week ago and am feeling like my old self again. Thanks.

Q. I had an elevated creatine level during a liver function test and my doctor recommended to cease creatine use.  Is this common?
     A. We have had reports of elevated creatinine levels and liver enzymes with heavy users of creatine, however since these were not controlled studies, we still are not sure. But this is one of the reasons why I believe in taking breaks from creatine use.

Q. Is taking creatine monohydrate the best way to gain weight and muscle if you a are a tall thin person?. I am wanting to gain weight and muscle, quite alot to be honest. Is there anything else I could do as well as taking creatine?. 
     A. Protein supplements, deep sleep, perhaps glutamine, and lots of time in the gym are helpful.

Q. I searched google and found your useful creatine monohydrate web site. Your web site is the solution to many of the questions regarding supplementing the creatine or any other food supplement. Thanks for such a nice web site. I am going to start using creatine Monohydrate Powder. I am doing weight lifting for the last 8 years and now I want to tone my body and burn some of the body fat and develop lean muscle mass. My weight is 96 kg. I want to know that if I mix creatine in a cold water with Glucose, is this better or should I mix creatine powder with some other drink.
     A. Creatine can be mixed with practically any solution, but my preference is fruit or vegetable juices since they are healthier.

Q. Can creatine supplement be effective without some sort of delivery system? In other words, if found in a whey protein supplement with no "delivery system," can it still provide benefits? Also, how much creatine per serving is needed to have an effect?
     A. Creatine works fine by itself, without anything else added to it. About 2 to 5 grams of creatine per serving should work well.

Q. I've been taking creatine for about a week or so now, and have gotten different answers from different people when I ask them, "Should I take creatine before or after I workout?". I would just like to know what you recommend. Thanks
     A. It's difficult to know for sure the ideal timing of creatine. Most likely both options work well. We haven't seen any research comparing the two options, therefore, at this time, you may wish to take creatine sometimes before, and other times after a workout.

Q. I know you can't give medical advice but I was wondering if you have ever heard of Creatine supplement use causing a higher than normal CPK level; for instance 1900?  I used the product Cell Tech which has 10g of Creatine per serving, but was off it for 7 weeks before having a CK test.  Any ideas would be helpful.
     A. CPK stands for creatine phosphokinase. There are several types of CPK. CPK--BB (CPK1) is found primarily in brain tissue, CPK--MB (CPK2) is found primarily in heart muscle, and CPK--MM (CPK3) is found primarily in skeletal muscle. It would be helpful to know which type your doctor can find. I don't think it's farfetched that creatine ingestion has a role in influencing CPK--MM, but I have not come across this finding yet until the issue is clarified.

Q. Dr. Sahelian, Hello!! I bought your book "CREATINE: Nature's Muscle Builder" about 6 years ago; second only to the BIBLE, this book helped me a great deal in achieving the results I saught. Doc, my question is regarding the shelf life of the following supplements: EAS Myoplex Delux protien, Betagen their creatine & HMB, Creatine HP, Next Nutrition's whey protien & Sport Pharma's Vanadyl & Thermadrene. I purchased these products & have a large quantity of them in my pantry (climate controlled in the house). They are 4-5 years old. Would you be afraid to consume them at this point in time? They still look & smell fine. I hate to waste all the money spent on them. In college I worked in a pharmacy & was told that after a drugs "expiration date" they didn't become poison, but over time their potency would decline.
     A. It is difficult to estimate expiration dates on supplements, but many of them can decompose and either not be as effective or potentially decompose into undesirable substances. Health is more important than money. It would be preferable to take fewer supplements but of higher quality and freshness.

Q. Thank you for providing such an informative web site on the benefits and side effects of creatine supplementation.  I have been supplementing with creatine monohydrate for almost 4 years and had not realized until after reading your site just how misguided my supplementation has been.  No article/publication that I have read to date has shed as much light on my experiences with creatine as yours....good and bad.  Much of my speculation regarding creatine over the years was either supported or confirmed in your Q&A section.  I never knew that so many other people had shared my experiences with the side effects of creatine.  I think we begin to wonder sometimes if we are imagining some of them.  And, thank YOU for providing excellent information as to the specifics of cause and effect.

Q. I like your informative web site. I just started taking Creatine and was on the loading dose for the first couple of days and got extremely depressed. I was not sure why till I read your Web Page. I stopped taking Creatine and I am feeling fine. I took creatine again just to see if I could recreate the experience as I felt physically strong and yes I got depressed. I feel you should warn you readers about this aspect of creatine. I have never had any problems mental or physical before.

Q. Does Creatine interfere with the metabolism or effect of any prescription drugs? May I add that I think your new book Mind Boosters is excellent and am impressed with the way you have combined your knowledge of previous books written about individual supplements into one volume.
     A. Thank you. Creatine has not been tested in combination with other medicines to find out if it alters their metabolism, but I don’t have any reasons to suspect that it would do so in any major way.

Q. Does creatine influence blood sugar, can diabetics take creatine?
     A. Diabetics have a tendency to have eventual kidney damage if their blood sugar is not well controlled. Creatine should not influence blood sugar to any significant extent, but since very high doses may harm the kidneys over the long run, someone who is diabetic should not take more than 1 gram of creatine a day. Creatinine blood levels should be monitored every few months.

Q. Please add my son's experience to your list of adverse behavioral effects using creatine. My athletic 18-yr old son plays varsity sports in high school: soccer, basketball, and lacrosse. He works out and lifts weights daily. He also ingests about 4g of creatine daily (Phosphagen). He does not take steroids or any other protein supplement. We have noticed that he has become extremely short-tempered, argumentative, and stressed out about the most trivial things. Because this behavior is also typical teenage behavior, it was difficult to make a connection between the creatine and the hot-headed-behavior until we talked with other parents who had experienced the same symptoms in their teenage sons who were also taking creatine. These parents also noticed a big improvement in their kids' temperaments after they stopped taking creatine. With a great deal of resistance, we are also making our son stop taking creatine, and we hope to see his less-difficult personality re-emerge--our friends indicated that it took about a month for them to see a change in behavior after their sons stopped taking the creatine.
     A. Although creatine may be the culprit, we should keep in mind that many people who take creatine are also taking other supplements, such as hormones or stimulants, that may cause irritability, or perhaps the particular creatine product was not pure.

Q. Hello Dr. I hope you remember who I am, I'm the guy who had been taking creatine for few years, but laid off for about few months due to injury. I then started my loading period of creatine for 1 month before taking a blood test resulting in liver inflammation, and promised to update you with the new results after 4 weeks.
Anyway I just now got the test results (after 4 weeks of not taking anything at all) from my liver blood test, the Dr said every thing is normal and there is no sign of liver inflammation.
     A. Thanks for the update, it seems that maybe your liver enzymes were elevated from the overuse of creatine and now they are back to normal after a period of being off creatine.

Q. I'm 16 and have high metabolism, I'm 6'2" tall and weigh 165. i'm really skinny and would like to build muscle but everything i try fails. Can you give me some pointers on gaining weight that i can turn into muscle? Would creatine help?
     A. Work out, work out, work out. Eat more protein, less junk carbs and bad fats, and use heavy weights with fewer repetitions. At this time I do not recommend creatine to teenagers unless supervised by their parents or physician.

Q. I have been using creatine off and on for 3 years and have noticed the following scenarios to be predictable. During the "creatine loading" dose week there is no doubt that I experienced a significant increase in muscle mass. I would say there is a drastic influence on muscle mass-- to the point that I'm not sure that I feel like "myself," after the loading week. I see casual photographs of myself that coincide with creatine loading and I look more like "angus" than approaching "aesthetic". I will attempt and lift heavier weights in squat, bench, and deadlift when loading creatine. And invariably, I wind up with an injury, (ie. low back or groin tear) that requires a several week set back. I will attempt longer and more challenging road bike rides in the mountains than I would usually tackle...and I will cramp during the last quarter of a 70 mile ride. It is always surprisingly painful to fight through the cramps and continue on.
     A. Thanks for the info about your creatine experience.

I was reading your creatine FAQ's and saw that you would be interested in hearing about temperaments associated with creatine use.  I have a friend who's husband was using 3-5 mg of creatine three times a week and no other supplements of any sort were being taken.  Within 2 weeks of taking creatine he became extremely edgy and his temper wouldn't just come out of no where but it would also become unmanageable.  They both consulted different internet groups and finally decided that he should discontinue creatine use.  It has been 4 months now and he has had no problems with his temperament or edginess. 

Q. I came across your site this weekend and I found your FAQ's on creatine to be very informative. Your site is the only site I have found that recommends only 3-4g of creatine every other day and taking a week off every month. 
        One of your FAQ's dealt with the possible psychological side effects of taking too much creatine. Although there is no conclusive proof that too much creatine may cause things like depression and anxiety attacks I can speak from personal experience that it caused me to experience both of those things. Two years ago I started taking 6-8g of creatine a day after the loading phase and other than occasional diarrhea I did not experience any problems. I did however gain size, some weight and the intensity of my workouts increased which is why I started taking creatine in the first place. Then about a year ago I  had rotator cuff surgery and could not work out for 6 months. When I started back lifting I also started to taking creatine again at the same dosages but began to experience anxiety attacks, the attacks continued until recently when quite by accident I found that within 2 hours after I took 6-8g of creatine I began to get depressed and anxious but on the days that I forgot to take creatine I was fine. I have since cut back my creatine intake to 3-4g every other day as your site suggests and I am no longer experiencing anxiety attacks.
        I thank God I found your site as I really thought I was going crazy.
     A. This is great information and many creatine users may be helped by reading about your personal experience.

Q. Very helpful creatine web page doctor. Answered many of my questions. 1,000 Thank yous to you.
     A. You're welcome.

Q. If creatine effects the size of muscles how does it affect your heart?
     A. I still don't have a good understanding, myself, on how creatine influences heart muscle. I would like to see studies evaluating cardiac size and function after creatine supplementation.

Q. I've been using creatine for about four years and I've never had anything bad to say about it but the other day my wife told me that at work a co-worker had told her that he had heard a report about creatine saying that creatine causes cancer is this true?
     A. Creatine is normally found in our bodies and some of the foods we eat, especially meats and fish. We ingest about a gram a day through food and another gram is made by the body. It is possible that high doses of creatine over prolonged periods could create toxins (creatine converts into creatinine) and cause harm to the body, and hence the smallest amount of creatine should be used to provide the necessary muscle gains. I am not aware of any studies that have shown creatine supplementation causing cancer in humans or animals.

I am an 18 year old creatine user. I have been using it for about 3 1/2 years. My parents and I have both noticed increased anger and irritability from the continued use of creatine. However, after short recesses in-between uses, the side-effects wore off. The side-effects have not been so bad as to stop me from using creatine, but I do think that if people are hot-tempered in nature, then they should exercise caution while using creatine for extended periods of time.

Q. If muscle mass is slowly decreased after the use of creatine if weight training is continued, then what is the point of creatine if you are back where you started before you started using the supplement?
     A. Good question. Creatine can be used at the start of an exercise program to motivate working out and overcoming the initial inertia that so often accompanies those who are just starting an exercise program. The motivation is due to the gains in muscle mass that come much quicker while on creatine. Many people don't stop using creatine completely but take 3 gm two to three times a week which seems to be enough to maintain the gain in muscle mass.

Are creatine supplements necessary for vegans?
Vegetarians, particularly those who are on a strict lacto-ovo-vegetarian (LOV) diet do not ingest much creatine since creatine is mostly found in meats, fish, and chicken. Creatine helps muscles stay firm and strong. In a study published in the Journal of Sports Nutrition and Exercise Metabolism, thirty-two healthy men, who regularly consumed an omnivorous diet, were split into two groups. One group consumed a LOV diet while the other group had an omnivorous diet (they ate everything). The study lasted 26 days. In addition to their diet, on day 22 of the study, subjects were assigned in a double-blind manner to receive either creatine monohydrate 0.3 g per kilogram of body weight per day or an equivalent dose of placebo for 5 days. The results demonstrated that consuming a LOV diet for 21 days decreased muscle creatine concentration in individuals who normally consume meat and fish. However, the creatine content of muscle in the LOV group returned back to normal after a period of only 5 days. Therefore, it appears that vegans could consider supplementing with about one gram of creatine per day.

Creatine Research Update
Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease.
Thorax. 2005 Jul;60(7):531-7.
Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. METHODS: Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). RESULTS: No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)). CONCLUSIONS: Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.

[Creatine deficiency syndromes]
Rev Neurol (Paris). 2005 Mar;161(3):284-9.
Creatine deficiency syndromes are a newly described group of inborn errors of metabolism affecting creatine metabolism. Three diseases have been described: deficiency of arginine: glycine amidinotransferase (AGAT), deficiency of guanidinoacetate methyltransferase (GAMT) and creatine transporter defect (CRTR). STATE OF ART: These syndromes are characterized by a depletion of creatine/phosphocreatine in the brain. Clinically, most of the patients develop a variable mental retardation and a severe speech delay associated with epilepsy, extra-pyramidal syndrome and behavior disturbances. These diseases are often diagnosed during infancy but a few adult cases have been reported recently. Diagnosis is established by measurement of guanidinoacetate and creatine in biologic fluids and in vivo proton magnetic resonance spectroscopy by the total lack of intra-cerebral creatine/phosphocreatine demonstrating. GAMT and AGAT deficiencies are treatable by oral creatine supplementation whereas patients with CRTR do not respond to the treatment.

Is the use of oral creatine supplementation safe?
J Sports Med Phys Fitness. 2004 Dec;44(4):411-6.
School of Sports Medicine, University of Trieste, Trieste, Italy.
This review focuses on the potential side effects caused by oral creatine supplementation on gastrointestinal, cardiovascular, musculoskeletal, renal and liver functions. No strong evidence linking creatine supplementation to deterioration of these functions has been found. In fact, most reports on side effects, such as muscle cramping, gastrointestinal symptoms, changes in renal and hepatic laboratory values, remain anecdotal because the case studies do not represent well-controlled trials, so no causal relationship between creatine supplementation and these side-effects has yet been established. The only documented side effect is an increase in body mass. Furthermore, a possibly unexpected outcome related to creatine monohydrate ingestion is the amount of contaminants present that may be generated during the industrial production. Recently, controlled studies made to integrate the existing knowledge based on anecdotal reports on the side effects of creatine have indicated that, in healthy subjects, oral supplementation with creatine, even with long-term dosage, may be considered an effective and safe ergogenic aid. However, athletes should be educated as to proper dosing or to take creatine under medical supervision.

Risk assessment of the potential side effects of long-term creatine supplementation in team sport athletes.
Eur J Nutr. 2004 Aug 11
Use of creatine has become widespread among sportsmen and women, although there are no conclusive evidences concerning possible health risks of long-term creatine supplementation. To investigate long-term effects of creatine monohydrate supplementation on clinical parameters related to health. Eighteen professional basketball players of the first Spanish Basketball League participated in the present longitudinal study. The subjects were ingesting 5 g creatine monohydrate daily during three competition seasons. Blood was collected in the morning after an overnight fast, five times during each of the three official competition seasons. Standard clinical examination was performed for 16 blood chemistries. RESULTS. The plasma concentrations of all clinical parameters did not alter significantly during the analyzed time frames of creatine supplementation. All of these parameters were, with the exception of creatinine and creatine kinase, within their respective clinical ranges at all time points. CONCLUSION. Our data shows that low-dose supplementation with creatine monohydrate did not produce laboratory abnormalities for the majority of the parameters tested.

Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy.
Neurology. 2004 May 25;62(10):1771-7.
To determine whether creatine monohydrate supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD). Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of creatine (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress , and bone degradation. RESULTS: During the creatine treatment phase, there was an increase in handgrip strength in the dominant hand and FFM, with a trend toward a loss of global muscle strength only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not creatine treatment, was associated with a lower 8-OH-2-dG/creatinine, and creatine monohydrate treatment was associated with a reduction in N-telopeptides. CONCLUSIONS: Four months of creatine supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.

Creatine supplementation in young soccer players.
Ostojic SM. Sports Medicine Institute, Yugoslavia. Int J Sport Nutr Exerc Metab. 2004 Feb;14(1):95-103.
The purpose of this study was to examine the effects of acute creatine-monohydrate supplementation on soccer-specific performance in young soccer players. Twenty young male soccer playersparticipated in the study and were matched and allocated to 2 randomly assigned trials: ingesting creatine-monohydrate supplement (3 x 10-g doses) or placebo for 7 days. Before and after the supplementation protocol, each subject underwent a series of soccer-specific skill tests: dribble test, sprint-power test, endurance test, and vertical jump test. Specific dribble test times improved significantly in the creatine group after supplementation protocol. Sprint-power test times were significantly improved after creatine-monohydrate supplementation as well as vertical jump height in creatine trial. Furthermore, dribble and power test times, along with vertical jump height, were superior in creatine versus placebo trialat post-supplementation performance. There were no changes in specific endurance test results within or between trials (p > .05). There were no between-trial differences in the placebo trial (p > .05). The main finding of the present study indicates that supplementation with creatine in young soccer players improved soccer-specific skill performance compared with ingestion of placebo.

Creatine monohydrate supplementation on body weight and percent body fat.
Kutz MR, Gunter MJ. Palm Beach Atlantic University, West Palm Beach, Florida 33416, USA.
J Strength Cond Res. 2003 Nov;17(4):817-21
Seventeen active males (age 22.9 +/- 4.9 year) participated in a study to examine the effects of creatine monohydrate supplementation on total body weight (TBW), percent body fat, body water content, and caloric intake. The TBW was measured in kilograms, percent body fat by hydrostatic weighing, body water content via bioelectrical impedance, and caloric intake by daily food log. Subjects were paired and assigned to a creatine or placebo group with a double-blind research design. Supplementation was given for 4 weeks (30 g a day for the initial 2 weeks and 15 g a day for the final 2 weeks). Subjects reported 2 days a week for supervised strength training of the lower extremity. Significant increases before and after the study were found in TBW and body water content for the creatine group. No significant changes were found in percent body fat or daily caloric intake in the creatine group. No significant changes were noted for the placebo group. These findings support previous research that creatine supplementation increases TBW. Mean percent body fat and caloric intake was not affected by creatine supplementation. Therefore weight gain in lieu of creatine supplementation may in part be due to water retention.

Creatine serum is not as effective as creatine powder for improving cycle sprint performance in competitive male team-sport athletes.
Gill ND, Hall RD. aikato Institute of Technology, Hamilton, New Zealand.
J Strength Cond Res. 2004 May;18(2):272-5.
This study examined the effects of supplementation with either creatine monohydrate powder in solution or a widely available creatine serum on performance in a repeated maximal sprint cycling test (10 x 6 seconds, 24-second passive rest between sprints). Using a randomized, double-blind, crossover design, 11 competitive male athletes supplemented with creatine in 2 forms according to the manufacturer's recommendations on 2 separate occasions. The 2 supplementation protocols were (a) 20 g.day(-1) x 6 days of creatine powder in solution plus a placebo serum (CP) or (b) 5 ml.day(-1) x 6 days of creatine serum plus a placebo powder (CS). Subjects completed 2 familiarization trials before the 6-day supplementation period. A repeated maximal sprint cycling test was performed prior to and immediately postsupplementation. A 7-week washout period separated the 2 supplementation protocols. Subjects' total work (9.6%) and peak power (3.4%) in the cycle sprint improved significantly (p < 0.05) after loading with creatine monohydrate powder, but there was little change after loading with creatine serum. The present data support previous research findings showing an ergogenic effect of creatine monohydrate powder supplementation but indicate that supplementation with creatine serum does not affect sprint cycling performance. Although the levels of creatine in each formulation were not determined, a substantial conversion of creatine into creatinine has been reported in many formulations and may explain the present findings.