Tag Archives: ATP

The Science of Creatine

 

During my time in the gym I’ve overhead numerous talk of creatine being illegal, a steroid, a protein, an ab-specific weight loss aid (eh??)…The list is endless and almost everything I’ve overheard is incorrect. I thought it would be useful to provide a clear piece of information that tells you what creatine actually is, how it impacts you on a physiological level, exaggerated side effects and if it can aid in your training.

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Creatine is perhaps the most well researched supplement on the market today.  Initially, fairly ‘low-dose’ creatine supplements where the norm but specific creatine supplements designed specially for strength training where not developed until the mid 1990s. The first such product was named Phosphagen by a company called EAS (1). Since then creatine supplements have exploded in popularity.

 

 


 

WHAT IS CREATINE?

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Creatine is a nitrogenous organic acid that aids in generating energy for cells, the most immportant being muscle cells. Creatine is not an essential nutrient and is produced naturally by the body from the amino acids glycine and arginine (2). The biosynthesis reaction is pretty tastey:

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Nothing boring about that...
Nothing boring about that…

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Almost all of this reaction occurs in the kidneys and liver. The produced creatine is then transported to skeletal muscle where the vast majority of it remains (3). Studies suggest as much as 50% of stored creatine in the muscles comes from dietary sources, mainly red meats, and that vegetarians possess significantly less natural creatine in their muscles than meat eaters (4) but levels are equal when both groups supplement (Get supplementing you veggies!)

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PHYSIOLOGICAL ROLE

 

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The importance of creatine in the body is highlighted by genetic disorders which disrupt the biosynthetic pathway pictured above. The major genetic disorders are associated with the synthesis enzymes or disruption of creatine transport into the brain (5,6). The end result of any of these genetic abnormalities is severe neurological defects suggesting creatine plays an important role in normal brain function (7). Additionally, research has shown that creatine supplementation provides not only physical enhancement but also cognitive improvements as well (8).

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Now for the important part: What does creatine actually do when it is sitting in the skeletal muscle? First we need to understand the power of ATP.

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All cells in our body utilise an ‘energy currency’ called ATP (Adenosine TriPhosphate) which we ultimately produce from the food we eat in the form of glucose (9). When energy is required in a cell a phosphate ion is split from the ATP molecule which then becomes ADP (Adenosine DiPhosphate). The breakdown of the last covelant link between phosphate and ATP liberates energy which can be utilised by the cell for a number of processes including movement, growth or protein synthesis (10)(In our case we want that cell to grow some big-ass biceps).

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Creatine itself can be phosphorylated into phosphocreatine with the addition of a phopshate ion take from ATP (12). Phosphocreatine comes into play by essentially acting as a phosphate store for when energy demands are high. At some point during exercise ATP is being reduced to ADP faster than ADP is restored to ATP. Our total ATP concentration is falling and thus so is our available energy. In the muscle, phosphocreatine is stripped of its precious phosphate which is then attached to a wandering ADP molecule. This provides a fresh new ATP molecule to power a cellular process.

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That is how creatine works as a supplement in a nut shell. It acts as a store of potential energy. The idea behind supplementing with large amounts of creatine is that we increase the creatine concentration in our muscles thus providing a larger store of energy which should allow for greater numbers of muscle contractions before we fatigue.

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Phopshate + Creatine (requires ATP) = Phosphocreatine

Phosphocreatine + ADP = Creatine + ATP       

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HOW WILL THIS AID MY TRAINING – WHAT DOES THE RESEARCH SHOW?

 

Creatine supplementation, in theory, provides a greater store of utilisable energy to skeletal muscle. This allows greater use of that muscle before the onset of muscle fatigue. In reality creatine supplementation is great for some types of exercise and fairly poor or non beneficial for others. Creatine will be of most use in high intensity anaerobic repetitive work (13). This would include something like weightlifting in which a number of repetitions are performed and then a break is taken. This can also include high intensity workouts involving rapid sprinting/cycling (14). Modest improvements have also been seen in ‘single effort work’ for example, a one rep max on a very heavy weight (15). In this area creatine has been shown to increase general performance with a focus on maximum power.

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Areas where creatine will not help at all are mainly endurance based sports, for example, long distance running (16). Presumably this is due to the fact that muscle activity is maintained for a long period of time and a lack of rest reduces ATP replenishment rates (ADP–>ATP) even when high levels of creatine are present in the muscle.

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'Is this how you do a bench press?'
‘Is this how you do a bench press?’

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To briefly summarise a number of other studies…It has been demonstrated that subjects receiving creatine supplementation along with resistance training lead to decreased serum myostatin concentrations compared to subjects that trained with no creatine or subjects which didn’t train and also didn’t receive any creatine (17). (Really we should have another group here that took creatine without doing resistance training but hey ho). Myostatin is important for INHIBITING muscle growth so a lack of it should allow for greater muscle development. Ever seen a Belgian Blue cow? These guys have been selectively bred to lack functional myostatin….

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Look at dat ass...
MOO BITCH

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Additional studies performed on young college footballers have also shown modest increases in circulating dihydro testosterone as well as testosterone itself following creatine supplementation (18.19) (please follow the references for greater detail). Creatine may therefore enhance your training in multiple ways, not just providing additional ATP for muscle contractions.

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Take home message: Creatine has no significant effect on aerobic endurance. However, it will increase power during short, repetition-based exercises including weight lifting and high intensity cardio training.

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COMMERCIAL FORMS

 

drugs

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Creatine can be purchased as a powder or as a tablet. I have always personally gone with a non-flavoured powder as it is easy to add to a protein shake. Tablets may be more convenient for people who want to take their creatine at a specific time when not at home. In terms of performance, both forms contain the same product but powdered creatine may provide faster absorption into the system. Make sure to read the manufacturers instruction when switching to a new creatine and always stay within the recommended dose.

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Something of additional importance to point out is that the supplement industry in general is always looking for ‘the next big thing’ to sell you. Very often ‘new and improved’ versions of creatine will make their way onto the market with loudly advertised improvements such as malate or citrate. These newer products offer no advantages over standard creatine but usually cost considerably more. Stick with standard creatine monohydrate (the form on which most research is based) for the same functional product at a lower cost.

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HOW AND WHEN TO TAKE CREATINE

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Most users of creatine, and most creatine product labels, suggest a loading phase followed by a maintenance phase of creatine dosing. The idea here is to saturate yourself (mainly your muscles!) with high levels of creatine in the first week followed by a lower dosing from then on. This is what I personally do whenever I have taken a break from creatine i.e. when going abroad for a week or two with limited weight training.

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It is common to see a cycle suggested on the product label. for example

Week 1: LOADING 5g x 4 times daily

Week 2-8 MAINTENANCE 5g daily

BREAK (usually 1-4 weeks)

REPEAT PROCESS

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It is not necessary to cycle creatine at all as it can be taken for a long period of time with no ill effect to health. However, most people throughout the year have commitments that may reduce or entirely remove their ability to train and this can be an opportunity to take a break from creatine and re-load when returning to the gym.

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SIDE EFFECTS AND HEALTH ISSUES

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One of the major things you may hear about creatine is in regards to it safety as a long-term supplement. Modern creatine-based supplements have only been around for two decades. Research can therefore only address this far back. Some studies looking into the health impacts of long term creatine use have lasted as long as five years. In most cases this is ample time to uncover any safety-related issues.

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Commonly cited 'side-effects' of creatine use such as kidney and liver damage, muscle cramps and dehydration have been thoroughly debunked in the literature

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Kidneys: Common statements seem to be that long term creatine use may lead to kidney and/or liver damage. Kidney damage is the most widely cited issue. This is probably due to research being portrayed in a misleading manner. When additional creatine is taken into the body, creatine breakdown products, namely creatinine, will also increase in the blood as well as in the urine. Serum creatinine levels are commonly used as an indicator but not direct measure of kidney function. Therefore, when supplementing with creatine, do not be alarmed by a rise in creatinine levels. Multiple human studies have confirmed that longer term creatine use is not damaging to the renal or hepatic systems in any way (20, 21, 22).

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kidneys

 

 

 

Gastro-intestinal Tract: GIT disruption CAN occur with larger doses of creatine, especially when taken on an empty stomach. This is sometimes referred to as ‘Mud Butt’ in some gyms. GIT disturbances are very rare, short lasting and self-resolving. These mild GIT issues can be avoided by taking smaller doses more frequently or eating something before hand. If you decide to cycle creatine and are starting the ‘load phase’ avoid taking your daily creatine all at once. Instead try to split dosing across the day.

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Heat tolerance and muscle cramping: Internet rumours suggesting creatine messes with thermoregulation, induces dangerous dehydration and/or muscle cramps have now been thoroughly debunked in two systematic reviews on the topic (23, 24)

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Weight gain: This is something that I actually found to be true but the weight gain I observed was probably due to water being pulled into the skeletal muscles. A number of studies have shown an acute increase in water retention in muscles following creatine loading but this subsides and has no negative effects on your training or health. Ultimately creatine has been shown more than once to promote FAT LOSS and lean MUSCLE MASS GAIN due to higher training intensities and volume (25,26).

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To date, research has found no negative impact to kidney, liver, intestinal function or any other major organ for that matter.In fact, in rodent studies, creatine improved the life span of mice (27) but whether this translates to humans remains to be seen. If you are a healthy individual then creatine is perfectly safe to take over the  long term. However,  it is important to point out that if you have a PRE-EXISTING KIDNEY DISORDER then it is probably best to avoid creatine-based supplements in general unless your doctor says otherwise.

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Take home message: Creatine can provide a real benefit to your workouts if you lift weights or perform high intensity cardio workouts. The supplement is cheap and safe to to take over a long period of time. Creatine comes in multiple forms but the standard powdered creatine monohydrate is the most popular for a reason.

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TOP PICKS

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I’ve tried a few different creatine manufacturers before. It can be an overwhelming choice as there are quite literally hundreds of different brands. However, on the inside of the tub its all essentially the same. My Protein Creatine monohydrate is very cheap and does a good job. It doesn’t dissolve well but I add it to my whey protein so don’t notice when drinking it. This is the stuff I’m currently using. The ‘micro-ionised’ powder by Optimum Nutrition dissolves much better so may be a good choice if you plan on taking the creatine by itself with water or juice. Creatine monohydrate can also come ‘flavoured’ which makes the experience of drinking it much more pleasant if just using water. My Protein offers a number of flavours and is a good place to start.

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Thanks for reading and please feel free to comment about your experiences with creatine whether good or bad. You can also reach me at ed@scienceguysupplements.com

-ScienceGuy





 

REFERENCES

I recommend using Google Scholar for quick access to these studies.

 

(1) Stoppani, Jim (May 2004). Creatine new and improved: recent high-tech advances have made creatine even more powerful. Here’s how you can take full advantage of this super supplement. Muscle & Fitness.

(2) “Supplement muscles in on the market”. National Review of Medicine. 2004-07-30

(3) Passwater, Richard A. (2005). Creatine. p. 9

(4) Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M; Chilibeck; Parise; Candow; Mahoney; Tarnopolsky (2003). “Effect of creatine and weight training on muscle creatine and performance in vegetarians”. Medicine and science in sports and exercise. 35(11): 1946–55.

(5) “L-Arginine:Glycine Amidinotransferase” http://omim.org/entry/602360

(6) Braissant, O; Henry, H; Béard, E; Uldry, J (May 2011). “Creatine deficiency syndromes and the importance of creatine synthesis in the brain.”. Amino Acids. 40 (5): 1315–24.

(7) Hemmer; W, Wallimann, T (1993) ”Functional aspects of creatine kinase in brain” Developmental Neuroscience. 15 (3-5): 249-260

(8) Rae, C; Digney A.L; McEwan S.R (June 2003). ”Oral creatin supplementation improves brain performance: a double blind, placebo controlled, cross-over trial”. Royal Society Publishing. 270, 2147–2150

(9) Knowles, J. R. (1980). “Enzyme-catalyzed phosphoryl transfer reactions”. Annu. Rev. Biochem. 49: 877–919.

(10) Campbell, Neil A.; Williamson, Brad; Heyden, Robin J. (2006). Biology: Exploring Life. Boston, MA: Pearson Prentice Hall.

(11) Di Carlo, S. E.; Collins, H. L. (June 1, 2001). “Submitting illuminations for review”. Adv. Physiol. Educ. 25 (2): 70–71

(12) Saks, Valdur (2007). Molecular system bioenergetics: energy for life. Weinheim: Wiley-VCH. p. 2.

(13) Bird, S. P. (2003). “Creatine Supplementation and Exercise Performance: A Brief Review” (PDF). Journal of Sports Science & Medicine. 2 (4): 123–132.

(14)  Graham, AS; Hatton, RC (1999). “Creatine: A review of efficacy and safety”. Journal of the American Pharmaceutical Association. 39 (6): 803–10; quiz 875–7.

(15)  Engelhardt, Martin; Neumann, Georg; Berbalk, Anneliese; Reuter, Iris (1998). “Creatine supplementation in endurance sports”. Medicine & Science in Sports & Exercise. 30 (7): 1123–1129

(16) Kreider R, Rasmussen C, Ransom J, Almada AL (1998). “Effects of creatine supplementation during training on the incidence of muscle cramping, injuries and GI distress”. Journal of Strength Conditioning Research. 12 (275).

(17)  Saremi, A.; Gharakhanloo, R.; Sharghi, S.; Gharaati, M.R.; Larijani, B.; Omidfar, K. (2010). “Effects of oral creatine and resistance training on serum myostatin and GASP-1”. Molecular and Cellular Endocrinology. 317 (1–2): 25–30

(18)  Van Der Merwe, Johann; Brooks, Naomi E; Myburgh, Kathryn H (2009). “Three Weeks of Creatine Monohydrate Supplementation Affects Dihydrotestosterone to Testosterone Ratio in College-Aged Rugby Players”. Clinical Journal of Sport Medicine. 19 (5): 399–404.

(19) Hoffman, J; Ratamess, N; Kang, J; Mangine, G; Faigenbaum, A; Stout, J (2006). “Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes”. International journal of sport nutrition and exercise metabolism. 16 (4): 430–46.

(20) Kreider, Richard B.; Melton, Charles; Rasmussen, Christopher J.; Greenwood, Michael; Lancaster, Stacy; Cantler, Edward C.; Milnor, Pervis; Almada, Anthony L. (2003). “Long-term creatine supplementation does not significantly affect clinical markers of health in athletes”. Molecular and Cellular Biochemistry. 244 (1–2): 95–104.

(21) Mayhew, DL; Mayhew, JL; Ware, JS (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 (4): 453–60

(22) Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert (2008). “Effects of creatine supplementation on renal function: A randomized, double-blind, placebo-controlled clinical trial”. European Journal of Applied Physiology. 103 (1): 33–40.

(23) Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM; Casa; McDermott; Ganio; Armstrong; Maresh (2009). “Does Creatine Supplementation Hinder Exercise Heat Tolerance or Hydration Status? A Systematic Review With Meta-Analyses”. Journal of Athletic Training. 44 (2): 215–23.

(24) Dalbo VJ, Roberts MD, Stout JR, Kerksick CM; Roberts; Stout; Kerksick (July 2008). “Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration”. British Journal of Sports Medicine. 42 (7): 567–73

(25) Antonio J, Ciccone V. The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength. Journal of the International Society of Sports Nutrition. 2013;10(1):36.

(26) Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc. 2000;32(3):654-658.

(27) Bender, A.; Beckers, J.; Schneider, I.; Hölter, S.M.; Haack, T.; Ruthsatz, T.; Vogt-Weisenhorn, D.M.; Becker, L.; et al. (2008). “Creatine improves health and survival of mice”. Neurobiology of Aging. 29 (9): 1404–11