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Christian Finn's Facts About Fitness

Creatine supplements: What works and what doesn't?

Most people wanting to build muscle, at one time or another, have either used or toyed with the idea of using creatine supplements. Unfortunately, in an industry dominated by hype and half-truths, independent and unbiased information about creatine is extremely hard to come by.

Pick up any health and fitness magazine, and you'll probably see numerous advertisements for the latest range of creatine supplements, with each new product promising to be more effective than the last. Unfortunately, because most magazines are either owned or supported financially (in the form of advertising) by supplement companies, getting to the truth can be extremely difficult.

Does the type of creatine you use really make that much of a difference? Can the benefits of creatine supplements like CELL-Tech® or Meta-CEL™ really justify the extra cost? Are the stories about creatine and its alleged side effects that appear in the popular press based on fact or fiction? And is there any truth to the rumor that creatine makes fat loss more difficult?

Creatine supplements
Discovered in 1832, your body forms creatine from three amino acids (glycine, arginine, and methionine) [2]. Once synthesized, creatine is transported to the muscle, heart and brain, where it's used as an energy source.

How does creatine work?

To understand how creatine works, it's important to know a little about where your body gets its energy from. Just like different countries throughout the world use different forms of currency, your body has its own energy currency. Known as adenosine triphosphate (or ATP for short), it provides energy for every move you make and every chemical reaction that occurs in your body.

ATP is constantly broken down and "re-created". Energy is released when one of the phosphates that form ATP is "broken off". During high-intensity exercise (such as a 60-meter sprint), the stores of ATP are depleted rapidly, and a quick method of reattaching the phosphate is required.

That's where creatine comes in. When your body stores creatine, some of it is attached to a phosphate group. Whenever ATP "loses" a phosphate, creatine "donates" one of its own to support the resynthesis of ATP.

The fatigue you experience during short bouts of high-intensity exercise (such as a 60-meter sprint) is linked with an inability of muscle to maintain a high rate of ATP resynthesis from creatine phosphate. In other words, if ATP is broken down more quickly than it can be resynthesized, you'll run out of energy.

Creatine supplementation increases the levels of creatine in muscle. Short-term creatine supplementation (15-30 grams per day for 5-7 days) increases total creatine stores by 15-30% and creatine phosphate levels by 10-40% [11].

Since the early 1990's, there are numerous studies to show that creatine can increase lean muscle mass, and improve performance during repeated bouts of short-term, high-intensity exercise (such as weight training) [25].

There are also reports that creatine has protective effects in heart, muscle and neurological diseases. In fact, several months of creatine supplementation reduces very-low-density lipoprotein levels (the so-called "bad" cholesterol) by almost one-third [8].

One of the main reasons creatine has become so popular is that it leads to rapid gains in lean tissue (but not necessarily muscle tissue) in a matter of days. In fact, research shows that just five days of creatine supplementation (20 grams daily) leads to a three-pound gain in lean tissue [15]. This initial gain in weight is probably due to an increase in water retention.

The benefits of creatine are also clear when it's used for several months. Jeff Volek and a research team from Pennsylvania State University showed that 12-weeks of creatine supplementation combined with a weight-training program accelerated gains in muscle size and strength compared to exercise alone [24]. Creatine users gained 24% more strength in the bench press, and 32% more in the squat. They also gained twice as much muscle.

Although the gain in weight during the first week of creatine supplementation is due to a rise in water weight, this increase in cell volume can increase protein synthesis while reducing protein breakdown — both of which are vital for muscle growth [12].

Creatine uptake
Despite its popularity, creatine alone does not work for everyone. Two or three people out of every 10 don't respond to supplementation (they're called — surprisingly enough — non-responders).

You've probably seen plenty of creatine formulas that promise to improve upon regular creatine. Supplements such as Phosphagen XT™ and CELL-Tech® are supposed to increase creatine uptake to a far greater extent than plain creatine.

Creatine uptake refers to the rise in the levels of creatine in the muscle. The degree of improvement in exercise performance is closely linked to creatine uptake. A rise of at least 20 mmol per kilogram of dry muscle is necessary before the benefits of supplementation become apparent [10].

The hormone insulin assists the transport of creatine into the muscle. Insulin aids the deposition of protein in cells by increasing the rate of amino acid transport through cell membranes. That's why combining creatine with an insulin-releasing agent (such as dextrose) can increase the rate of creatine uptake during supplementation.

Some evidence for this comes from a research team based at Queen's Medical Center, Nottingham [20]. They compared a high-carbohydrate (94 grams) solution with a mixture of protein (50 grams) and carbohydrate (47 grams).

After consuming creatine with 94 grams of carbohydrate, creatine uptake was around 48%. What this means is that for every 10 grams of creatine, just under five grams was retained. This was identical to the amount of creatine that was retained following the consumption of 50 grams of protein and 47 grams of carbohydrate.

CELL-Tech® is just one creatine supplement designed to take advantage of the fact that the rate of creatine uptake is increased when it's taken with carbohydrate. CELL-Tech® also contains a number of other ingredients, such as taurine, ascorbate (vitamin C), chromium picolinate, alpha-lipoic acid, phosphorus, sodium, calcium and magnesium.

In one trial, a group of male subjects was assigned to one of two groups. Both groups trained with weights for one hour, six days a week for eight weeks. The first received CELL-Tech®, while group two was given a supplement containing a combination of protein and carbohydrate (10 grams of casein and 75 grams of glucose) after exercise [39].

The average gains in lean muscle were greater in the group using CELL-Tech® (8.8 pounds) compared with the protein-carbohydrate group (5.7 pounds). Despite claims that CELL-Tech® is the "biggest industry breakthrough in creatine supplementation", this extra three-pound gain in weight is no greater than you'd expect with five days of plain creatine supplementation (20 grams daily) [10].

When they were tested for maximal strength at the end of the study, increases in strength were greater for the CELL-Tech® group in seven of the exercises, greater for the protein-carbohydrate group in six of the exercises, and identical for the other three.

Carbohydrate
More recently, the popularity of low-carbohydrate diets has prompted supplement companies to look for other ways to enhance the rate of creatine uptake without large amounts of carbohydrate. One of the most recent supplements to hit the market is a product called Meta-CEL™. Along with creatine, a small amount of carbohydrate, sodium bicarbonate, sodium chloride, and citrus aurantium extract, Meta-CEL™ contains a compound found in certain plants, trees and foods called D-Pinitol.

One study shows that taking creatine with low doses of D-Pinitol works as well as carbohydrate and protein at increasing the rate of creatine uptake. Despite this, Meta-CEL™ offers very little benefit compared to regular creatine.

That's because the addition of various "insulin potentiators" or patented "transport systems" do not increase creatine uptake. Rather, they increase the rate of uptake. When they use it for the first time, most people "load" with 20-30 grams of creatine each day for the first week. One reason creatine loading is so popular is because it raises creatine levels very rapidly. However 30 days of low-dose creatine supplementation raises the concentration of creatine in your muscles to the same extent as seven days using higher doses.

For example, six days of creatine supplementation (20 grams per day) leads to a 20% rise in muscle creatine concentration [13]. It's possible to maintain this elevated level with just two grams of creatine per day. But you can get the same rise in creatine levels with just three grams of creatine per day for 30 days.

Your body has a "pool" of creatine. Supplementation helps to increase the amount of creatine in that pool. And, just like a swimming pool can only hold so much water, there's only so much creatine your body can store.

Imagine you were using a hose to fill a swimming pool. You could open the tap up fully, and the pool would fill with water more quickly. Or, you could leave the tap partially closed, in which case the pool would take longer to fill. But once the pool is full, extra water is simply wasted. It's the same with creatine and your muscles. Once your muscles are saturated with creatine, any excess is lost in the urine.

In other words, if you plan to use creatine for 30 days or longer, there's little need to load with creatine, or even to use an "advanced" creatine supplement designed to speed the rate of uptake. Dr. Mark Tarnopolsky, in a presentation at the American College of Sports Medicines' Health and Fitness conference, also points out that creatine loading is unnecessary. According to Tarnopolsky, three grams of creatine daily is enough to keep the muscle saturated.

Exercise
Exercise also increases the rate of creatine uptake [18]. A research group led by Professor Roger Harris showed that levels of creatine following supplementation in the muscles of an exercised leg rose by 38%. In the rested leg, creatine levels only increased by 26% [11].

So, it appears that the best time to use creatine is after exercise. There is no benefit of taking creatine before exercise [33]. In fact, creatine taken during (or slightly before) exercise appears to "interfere" with the performance gains linked with prior creatine loading [21].

Another factor affecting your response to creatine is the level of creatine in the muscles before you start supplementation [11]. Foods such as herring, salmon, tuna, beef and pork all contain in excess of four grams of creatine per kilogram [2].

Because they don't eat meat or fish (two foods that contain creatine), vegetarians usually respond well to supplementation, as they often have very low levels of creatine in their muscle cells to begin with [6].

Cycling

Many people choose to cycle creatine, using it for a number of months before discontinuing its use for several weeks. Cycling creatine is based on the theory that your body eventually becomes "resistant" to the beneficial effects of supplementation. However, there's no research to show this is necessary.

Animal studies show that large doses of creatine given to animals for three months down regulates (makes less active) the parts of a cell that transport creatine into the muscle. However, the amounts of creatine (1-2 grams per kilogram of bodyweight daily — the equivalent of 70-140 grams of creatine for someone weighing 70 kilograms) are far higher than those used in most studies. The same doesn't hold true in humans using lower doses.

One trial, led by Dr. Mark Tarnopolsky, shows that four months of creatine supplementation (0.075 grams per kilogram of bodyweight daily — the equivalent of five grams daily for someone weighing 70 kilograms) does not alter creatine transporter protein content [29]. Dr. Jeffrey Stout, assistant professor at Creighton University and co-director of the human performance research lab, says he hasn't stopped using creatine since 1994!

Limitations
Although the research supporting the benefits of creatine as an aid to muscle growth is pretty solid, the news isn't all good.

High doses of caffeine also appear to "block" the effects of creatine [22]. Creatine and caffeine taken together both raise muscle creatine phosphate levels to the same extent as creatine supplementation only, whereas it was only the latter treatment that improved performance.

That said, the study in question used very large doses of caffeine (five milligrams of caffeine per kilogram of bodyweight). Moreover, previous research has used creatine dissolved in warm caffeinated drinks, such as coffee or tea. As such, it's likely that only very high doses of caffeine should cause concern.

Creatine supplementation has little effect on performance in multiple sprints lasting 6-60 seconds when long recovery periods (5-25 minutes) are used between sprints [4]. For example, creatine improves performance when short bouts of high-intensity cycling are separated by 30 seconds of rest [1]. When the rest period is extended from 30 to 120 seconds, performance is not affected [17].

What this means is that the beneficial effect creatine has on performance will become less apparent with longer rest periods (greater than 60 seconds) between bouts of exercise [3].

There are also concerns that creatine will make it harder for you to lose fat. This is based on the results of a trial carried in the Journal of Applied Physiology [40]. Ten active men taking part in a resistance-training program were given either creatine (20 grams per day for four days, then two grams for 17 days) or a placebo for several weeks.

When they used the placebo, the men lost an average of five pounds of fat. However, there was no significant change in body fat when they used creatine. The results also show that creatine led to a 9% rise in the number of carbohydrate calories burned for energy, and a drop in the use of stored fat.

Although they're certainly interesting, these results need to be replicated in a few other studies before we can come to any conclusions about creatine and fat loss. Still, if you're having a hard time losing fat, it might be worth dropping creatine from your nutrition program for a few months to see what difference it makes.

Performance
Whether creatine improves athletic performance outside of the laboratory is open to debate. If a lack of muscle mass is limiting your performance, then creatine certainly has the potential to help you perform better. However, in many sports, there's an "optimum" amount of muscle size, beyond which adding additional muscle bulk may be counterproductive. In short, bigger muscles don't always translate to superior performance.

It's also true that creatine can enhance your performance during short, repeated bouts of high-intensity exercise. A group of Spanish researchers, for instance, showed that creatine improves performance in a series of tests designed to match the activity of a competitive soccer game.

Publishing their findings in the journal Medicine and Science in Sports and Exercise, the researchers tested a group of players from Athletic Club de Bilbao, one of Europe's leading soccer teams [16]. The players were divided into two groups. Group one was given 20 grams of creatine per day for six days. Group two received a dummy supplement that had no effect. Creatine resulted in faster sprinting times, and also improved jumping performance.

Researchers from the University of Western Australia also believe that creatine has the potential to improve athletic performance [27]. They took a group of active (but not well-trained) men, and asked them to perform a series of bike sprints for 80 minutes. The test was designed to mimic the physical demands of sports such as soccer, or field hockey. After completing the test, the men were split into two groups. One group took 20 grams of creatine daily, while group two was given a placebo.

Five days later, the men took the test again. Results showed that the total amount of work performed increased by 6% in the creatine group. No such improvements were found in subjects using the placebo. The creatine group also outperformed their colleagues in the middle and latter stages of the test.

However, it's important to remember that both of these studies involved simulated tests designed to mimic the demands of a certain sport. A soccer player starting supplementation with creatine, for example, can expect to gain several pounds in weight. This extra weight could slow him down during a 90-minute game. In fact, there is evidence to show that creatine may impair performance during endurance exercise — when cross-country runners used creatine, their times actually got worse [28].

Side effects
There are claims that creatine users are more susceptible to cramps, muscle spasms, and even pulled muscles. However, three-years of creatine supplementation had no effect on the incidence of injury or cramping in college American footballers [34].

Research published in the journal Medicine and Science in Sports and Exercise shows similar results [35]. In a group of 26 athletes (18 men and 8 women) using creatine for up to four years, there was no difference in the reported incidence of muscle cramp or injury compared with athletes not using creatine.

When I started using creatine in 1996, I can still remember one occasion when I suffered from extremely painful muscle cramps. After teaching a 45-minute exercise class in a hot and humid swimming pool hall, the first thing I should have done was get something to drink. But I didn't. Instead, I went straight into the office and sat down to read a newspaper.

Suddenly, the back of my left thigh started to cramp up. So, I straightened my leg to try and ease the pain. Then, the front of my thigh started to cramp as well. I didn't know what to do. I couldn't bend or straighten my leg — so I just sat there hoping the pain would go away.

Of course, I have no idea whether or not creatine contributed to the problem. Scientists aren't really sure what causes cramp in the first place. But up until then, I'd never experienced such painful cramps in the front and back of my thigh at the same time. Now, I always make sure to carry a bottle of water with me when I go to the gym.

There are isolated case reports of individuals suffering adverse effects after using creatine [30, 31]. Yet, carefully controlled studies over the short- (five days), medium- (nine weeks) and long-term (up to five years) have yet to demonstrate that creatine supplementation has any adverse effects on blood pressure, kidney or liver function [15, 32, 35, 36, 37].

Studies focusing on the medical applications of creatine using continuous low doses (less than two grams per day) for up to five years show no adverse side effects [19, 23]. Of course, an absence of evidence is not evidence of absence. The fact no side effects have been found doesn't mean none exist. People with existing liver or kidney problems, or those predisposed to such ailments, should seek medical advice before using creatine [38].

The bottom line
Based on the research to date, there's very little evidence to suggest that creatine needs to be loaded. Smaller doses (3-5 grams) taken over 30 days will saturate your muscles with creatine to the same degree as 20 grams taken for six days.

Although creatine has the potential to improve performance in certain sports, the rapid gain in weight could make things worse rather than better. The only way to find out is to try it for yourself. Thirty days of low-dose creatine supplementation (0.027 grams per pound) will lead to a gradual gain in weight, giving your body more time to get used to the extra mass.

The best time to take creatine appears to be after exercise. Not only does this increase the rate of creatine uptake, but it also increases glycogen levels (glycogen is the name given to carbohydrate stored in your muscles). Approximately 0.06 grams of creatine per kilogram of weight (or 0.027 grams per pound) should be sufficient to raise creatine levels.

Small amounts of creatine (one gram or less) have little effect on creatine levels in the blood. Higher doses (five grams) increase levels fifteen-fold [11]. So, someone weighing 120 pounds would consume around three grams of creatine after exercise. A 220-pound individual, on the other hand, would consume roughly six grams.

The way creatine promotes muscle growth over a period of several months is still the subject of some debate. It's likely to work by increasing protein synthesis, reducing protein breakdown, or increasing the amount of work you can perform in each workout. Probably, it's a combination of all three. Because creatine promotes an anabolic environment favoring muscle growth, continuous low-dose supplementation may be more effective than the common practice of cycling creatine.

There's also very little evidence to suggest that effervescent, or micronized creatine products offer any advantages over plain creatine monohydrate. While supplement companies will continue to promote their "advanced" creatine blends, there's only so much creatine your muscles can store. Once creatine levels reach their upper limit, any excess will be simply flushed down the toilet.

References
1. Balsom, P.D, Ekblom, K., Soderlund, B., & Ekblom, B. (1993). Creatine supplementation and dynamic high-intensity intermittent exercise. Scandinavian Journal of Medicine and Science in Sports, 3, 143-149
2. Balsom, P.D., Soderlund, K., & Ekblom B. (1994). Creatine in humans with special reference to creatine supplementation. Sports Medicine, 18, 268-280
3. Bogdanis, G.C., Nevill, M.E., Boobis, L.H., & Lakomy, H.K. (1996). Contribution of phosphocreatine and aerobic metabolism to energy supply during repeated sprint exercise. Journal of Applied Physiology, 80, 876-884
4. Burke, L.M., Pyne, D.B., & Telford, R.D. (1996). Effect of oral creatine supplementation on sibgle-effort sprint performance in elite swimmers. International Journal of Sport Nutrition, 6, 222-233
5. Casey, A., Constantin-Teodosiu, D., Howell, S., Hultman, E., & Greenhaff, P.L. (1996). Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. American Journal of Physiology, 271, E31-E37
6. Delanghe, J., De Slypere, J.P., De Buyzere, M., Robbrecht, J., Wieme, R., & Vermeulen, A. (1989). Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clinical Chemistry, 35, 1802-1803
7. Earnest, C.P., Snell, P.G., Rodriguez, R., Almada, A.L., & Mitchell, T.L. (1995). The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta physiologica Scandinavica, 153, 207-209
8. Earnest, C., Almada, A., & Mitchell, T. (1996). High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clinical Science, 91, 113-118
9. Green, A.L., Simpson, E.J., Littlewood, J.J., Macdonald, I.A., & Greenhaff, P.L. (1996). Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiologica Scandinavica, 158, 195-202
10. Greenhaff, P.L., Bodin, K., Soderlund, K., & Hultman, E. (1994). Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. American Journal of Physiology, 266, E725-E730
11. Harris, R.C, Soderlund, K., & Hultman, E. (1992). Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science, 83, 367-374
12. Haussinger, D. (1996). The role of cellular hydration in the regulation of cell function. Biochemical Journal, 313, 697-710
13. Hultman, E., Soderlund, K., Timmons, T.A., Cederblad, G., & Greenhaff, P.L. (1996). Muscle creatine loading in men. Journal of Applied Physiology, 81, 232-237
14. Kreider, R.B., Ferreira, M., Wilson, M., Grindstaff, P., Plisk, S., Reinardy, J., Cantler, E., & Almada, A.L. (1998). Effects of creatine supplementation on body composition, strength and sprint performance. Medicine and Science in Sports and Exercise, 30, 73-82
15. Mihic, S., MacDonald, J.R., McKenzie, S., & Tarnopolsky, M.A. (2000). Acute creatine loading increase fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medicine and Science in Sports and Exercise, 32, 291-296
16. Mujika, I., Padilla, S., Ibanez, J., Izquierdo, M., & Gorostiaga, E. (2000). Creatine supplementation and sprint performance in soccer players. Medicine and Science in Sports and Exercise, 32, 518-525
17. Redondo, D.R., Dowling, E.A., Graham, B.L., Almada, A.L., & Williams, M.H. (1996). The effect of oral creatine monohydrate supplementation on running velocity. International Journal of Sport Nutrition, 6, 213-221
18. Robinson, T.M., Sewell, D.A., Hultman, E., & Greenhaff, P.L. (1999). Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle. Journal of Applied Physiology, 87, 598-604
19. Sipila, I., Rapola, J., Simell, O., & Vannas, A. (1981). Supplementary creatine as a treatment for gyrate atrophy of the chloroid retina. New England Journal of Medicine, 304, 867-870
20. Steenge, G.R., Simpson, E.J, & Greenhaff, P.L (2000). Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. Journal of Applied Physiology, 89, 1165-1171
21. Vandebuerie, F., Vanden Eynde, B., Vandenberghe, K., & Hespel, P. (1998). Effect of creatine loading on endurance capacity and sprint power in cyclists. International Journal of Sports Medicine, 19, 490-495
22. Vandenberghe, K., N. Gillis, M. Van Leemputte, P. Van Hecke, F. Vanstapel, and P. Hespel. (1996). Caffeine counteracts the ergogenic action of muscle creatine loading. Journal of Applied Physiology, 80, 452-457
23. Vannas-Sulonen, K., Sipila, I., Vannas, A., Simell, O., & Rapola, J. (1985). Gyrate atrophy of the chloroid and retina: a five year follow-up of creatine supplementation. Opthalmology, 91, 1719-1727
24. Volek J.S., Duncan, N.D., Mazzetti, S.A., Staron, R.S., Putukian, M., Gomez, A.L, Pearson, D.R, Fink, W.J., & Kraemer WJ. (1999). Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Medicine and Science in Sports and Exercise, 31, 1147-1156
25. Volek, J.S., & Kraemer W.J. (1996). Creatine Supplementation: Its effect on human muscular performance and body composition. Journal of Strength and Conditioning Research, 10, 200-210
26. Williams, M.H., & Branch, J.D. (1998). Creatine supplementation and exercise performance: An update. Journal of the American College of Nutrition, 17, 216-234
27. Preen, D., Dawson, B., Goodman, C., Lawrence, S., & Beilby, J. (2001). Effect of creatine loading on long-term sprint exercise performance and metabolism. Medicine and Science in Sports and Exercise, 33, 814-821
28. Demant, T.W., & Rhodes, E.C. (1999). Effects of creatine supplementation on exercise performance. Sports Medicine, 28, 49-60
29. Tarnopolsky, M., Parise, G., Fu, M.H., Brose, A., Parshad, A., Speer, O., & Wallimann, T. (2003). Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans. Molecular and Cellular Biochemistry, 244, 159-166
30. Koshy, K.M., Griswold, E., & Schneeberger, E.E. (1999). Interstitial nephritis in a patient taking creatine. New England Journal of Medicine, 340, 814-815
31. Pritchard, N.R., & Kalra, P.A. (1998). Renal dysfunction accompanying oral creatine supplements. Lancet, 351, 1252-1253
32. Poortmans, J.R., & Francaux, M. (2000). Adverse effects of creatine supplementation: fact or fiction? Sports Medicine, 30, 155-170
33. Preen, D., Dawson, B., Goodman, C., Lawrence, S., Beilby, J., & Ching, S. (2002). Pre-exercise oral creatine ingestion does not improve prolonged intermittent sprint exercise in humans. Journal of Sports Medicine and Physical Fitness, 42, 320-329
34. Greenwood, M., Kreider, R.B., Melton, C., Rasmussen, C., Lancaster, S., Cantler, E., Milnor, P., & Almada, A. (2003). Creatine supplementation during college football training does not increase the incidence of cramping or injury. Molecular and Cellular Biochemistry, 244, 83-88
35. Schilling, B.K., Stone, M.H., Utter, A., Kearney, J.T., Johnson, M., Coglianese, R., Smith, L., O'Bryant, H.S., Fry, A.C., Starks, M., Keith, R., & Stone, M.E. (2001). Creatine supplementation and health variables: a retrospective study. Medicine and Science in Sports and Exercise, 33, 183-188
36. Kreider, R.B., Melton, C., Rasmussen, C.J., Greenwood, M., Lancaster, S., Cantler, E.C., Milnor, P., & Almada, A.L. (2003). Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Molecular and Cellular Biochemistry, 244, 95-104
37. Mayhew, D.L., Mayhew, J.L., & Ware, J.S. (2002). Effects of long-term creatine supplementation on liver and kidney functions in American college football players. International Journal of Sport Nutrition and Exercise Metabolism, 12, 453-460
38. Wyss, M., & Kaddurah-Daouk, R.(2000). Creatine and creatinine metabolism. Physiological Reviews, 80, 1107-1213
39. Tarnopolsky, M.A., Parise, G., Yardley, N.J., Ballantyne, C.S., Olatinji, S., & Phillips, S.M. (2001). Creatine-dextrose and protein-dextrose induce similar strength gains during training. Medicine and Science in Sports and Exercise, 33, 2044-2052
40. Huso, M.E., Hampl, J.S., Johnston, C.S., & Swan, P.D. (2002). Creatine supplementation influences substrate utilization at rest. Journal of Applied Physiology, 93, 2018-2022
41. Derave, W., Eijnde, B.O., Verbessem, P., Ramaekers, M., Van Leemputte, M., Richter, E.A., & Hespel, P. (2003). Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans. Journal of Applied Physiology, 94, 1910-1916
42. Rooney, K.B., Bryson, J.M., Digney, A.L., Rae, C.D., & Thompson, C.H. (2003). Creatine supplementation affects glucose homeostasis but not insulin secretion in humans. Annals of Nutrition and Metabolism, 47, 11-15