The Ultimate Guide To Creatine Supplementation Part 2

In the Part 1 of this series, I explained what creatine is and what it does in the body. The details may seem unimportant. Most of the so-called “experts” seem to think that. But in order to understand and interpret the science, we need to understand creatine at the most basic level so we can correctly interpret what researchers observe, allowing us to develop the most beneficial protocols instead pulling something out of our ass.

Now that we know what creatine is and what it does at the cellular level, in this section let’s look at what supplementing with creatine can do for you.

Muscular Hypertrophy

Let’s face facts. Creatine didn’t make such a massive splash in the supplement industry because of its ability to bridge energy systems and possibly help with getting one or two reps more than normal. Creatine supplementation is touted as an extremely effective muscle builder, and research supports this wholeheartedly[1-10] and this has been verified through meta-analysis[11].

The myth spread by people who think any mass-market supplement must be junk—like your doctor—is that creatine supplementation doesn’t increase lean body mass, but only increases fluid retention. If you’re lucky, your neighborhood bro-scientist will tell you the same thing. This is false. Creatine supplementation has been shown to cause a net flow of extra fluid into cells and even into the space between cells[5,12]. These intra- and extra-cellular pools do increase in fluid content[13-15], but creatine does, in fact, increase muscle mass.

What’s more curious is that even in the absence of resistance training, creatine supplementation can increase lean body mass[10].

Creatine Is Anabolic

Remember, your body is in a constant state of protein turnover. It’s constantly tearing down muscle tissue, then rebuilding it. The normal turnover rate for a lean, healthy individual is roughly 0.36 grams of protein per pound of body weight (0.8g/kg)[16-17]. This means that a lean 200 pound male would need to consume at least 72 grams of protein per day simply to maintain body mass.

Illustration of muscle fiberIf we shift this balance—even in the absence of resistance training—so the protein turnover is less, and more protein is synthesized than destroyed, it would be possible to gain muscle taking in a small amount of protein. This is typically how anti-catabolic agents work. They don’t increase growth signals per se, but they slow muscle protein breakdown. This is likely how creatine works to increase muscle size.

Creatine shifts the body’s metabolism to grow more muscle by doing both: increasing muscle protein synthesis and decreasing muscle protein breakdown. Specifically, creatine enhances growth of myosin heavy chain (MHC) type I and particularly type II fibers[18-20]. MHC type II fibers are the “fast twitch” muscle most responsible for the extreme amounts of muscle mass that one can achieve through resistance training[21-22]. This is particularly true for MHC IIa and IIx fibers[23].

 (NOTE: You may have expected me to talk about MHC type IIb fibers, like everyone else, including medical texts, but humans don’t actually express the super-fast twitch fibers, type IIb. We possess a slightly slower counterpart called type IIx[24].)

Creatine is Anti-Catabolic

Like I said, we can increase hypertrophy of muscle tissue in one of two ways, by increase muscle protein synthesis—the anabolic process—and by decreasing muscle protein breakdown—the catabolic process. As I described, creatine is definitely anabolic by shifting toward greater protein synthesis. Creatine also slows muscle protein breakdown.

Creatine has been shown to decrease myostatin, one of the most catabolic and size-limiting genes in the human body[25]. By decreasing activation, you get a bump in the maximum size you can obtain. Theoretically, though, it should reach maximum effectiveness quickly. This coincides with the current rate of research, and it explains why creatine supplementation can be used to prevent muscle wasting during old age and cancer treatment[26-27].

Dennis Wolf has just about all the carbs and creatine stuffed into his muscles that he can.

Dennis Wolf has just about all the carbs and creatine stuffed into his muscles that he can.

Creatine, Glycogen, and GLUT4

Creatine has a few more tricks up its powdery sleeve—ones that make it a prime candidate for use with Carb Back-Loading and even Carb Nite. Research has shown that creatine supplementation can increase muscle GLUT4 expression for up to 24 hours after resistance training above normal[20, 28-30]. If you’ve read Carb Back-Loading 1.0—or any of my many readily available articles about CBL—you already understand the importance of this. In short, the more GLUT4 transporters a muscle has, the greater its ability to absorb glucose, replenish glycogen stores, and prevent fat cells from storing glucose as part of body fat.

Researchers have also demonstrated that creatine supplementation can allow for supercompensation of glycogen levels within muscles, but only with resistance training.

And, on the flip-side, ingesting carbs can increase the retention of creatine levels within muscles[31-33].  So if you’re Carb Back-Loading, the creatine boosts the response to carbs (in terms of glycogen storage) and the carbs boost the creatine retention. This makes creatine the ideal supplement on Carb Back-Loading and on Carb Nites.

There’s also another benefit to creatine supplementation that I find interesting and that could be of use with cyclic-ketogenic diets like CBL and Carb Nite. After supplementing for a couple of weeks with creatine, the body burns more glucose than normal while at rest[45]. Now it’s hard to say how this research translates from the case studied–the participants all ate a standard mixed diet–but if it does hold true, then through the non-carb portions of the day, the body may clear out glucose reserves faster. On Carb Nite, this would be beneficial because your body will get back into a pure ketogenic state faster. On CBL, however, this could cause problems. To date, no negative effect of creatine on body composition has been reported, so it’s probably not something worth worrying about on CBL, but it might be worth a shot at accelerating results with Carb Nite.

Brain Boost 

Every cell in your body has mitochondria along with a creatine/creatine phosphate transport system, including the cells of the nervous system. By allowing an efficient and low-cost recycling system for ATP, creatine keeps cells running smoothly and allows them to navigate short-lived energy demands as though nothing has happened. This is true even in brain cells[34-35]. In a study that tested creatine supplementation in vegetarians, cognitive function was found to increase[36-37]. This isn’t surprising, because vegetarians and vegans don’t eat the primary dietary source of creatine—meat—and have lower level than omnivores[38]. This is also likely why you never see vegans competing at a world-class level in power sports like sprinting or powerlifting.

Creatine also helps fight against cognitive decline with age[39].


zombie_food_by_tether_cat-d4g85eeThere’s evidence in rat models that suggests that creatine could increase lifespan[40-41]. Since we now know what creatine actually does in cells, this isn’t a surprising discovery. If your mitochondria don’t need to do the extra work of converting ADP directly into ATP, we actually get a lower production of metabolic waste products. I’m referring specifically here to positive ion carriers, which can put stress on the cellular machinery. The buildup of positive ion carriers is what causes fatigue in muscles, not excess lactate. Free potassium (K+), magnesium (Mg+2) and calcium (Ca+2) along with free hydrogen (H+, what lowers pH and increases acidity), are the sources of muscular fatigue[42-44].

By supplementing with creatine, we prevent this excess mitochondrial respiration from activating—except during periods of physical exertion. During these periods, these effects can be beneficial—as you can see when you open any physique-oriented magazine and look at what results.

Coming Up Next…

Obviously, creatine is a super supplement, we just need to know the best way to supplement. Because of all the questions I’ve received about the type, timing and amounts of creatine to ingest, I’ve written what would be an overwhelming amount of information for a single post. So, want to know how much creatine to take and which kind is best? Come back next week. Same Bat-time, same Bat-channel. 

The Ultimate Guide To Creatine Supplementation Part 1 

The Ultimate Guide To Creatine Supplementation Part 3


  1. Candow DG, Chilibeck PD, Chad KE, Chrusch MJ, Davison KS, Burke DG. Effect of ceasing creatine supplementation while maintaining resistance training in older men. J Aging Phys Act. 2004 Jul;12(3):219-31.
  2. Saremi A, Gharakhanloo R, Sharghi S, Gharaati MR, Larijani B, Omidfar K. Effects of oral creatine and resistance training on serum myostatin and GASP-1. Mol Cell Endocrinol. 2010 Apr 12;317(1-2):25-30.
  3. Volek JS, Ratamess NA, Rubin MR, Gómez AL, French DN, McGuigan MM, Scheett TP, Sharman MJ, Häkkinen K, Kraemer WJ. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004 May;91(5-6):628-37.
  4. Bemben MG, Lamont HS. Creatine supplementation and exercise performance: recent findings. Sports Med. 2005;35(2):107-25. Review.
  5. Balsom PD, Söderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med. 1994 Oct;18(4):268-80. Review.
  6. van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond). 2003 Feb;104(2):153-62.
  7. Cooke WH, Grandjean PW, Barnes WS. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. J Appl Physiol. 1995 Feb;78(2):670-3.
  8. Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am J Physiol. 1996 Nov;271(5 Pt 1):E821-6.
  9. Mujika I, Chatard JC, Lacoste L, Barale F, Geyssant A. Creatine supplementation does not improve sprint performance in competitive swimmers. Med Sci Sports Exerc. 1996 Nov;28(11):1435-41.
  10. van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond). 2003 Feb;104(2):153-62.
  11. Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003 Jun;13(2):198-226.
  12. Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clin J Sport Med. 1998 Oct;8(4):298-304. Review.
  13. Easton C, Turner S, Pitsiladis YP. Creatine and glycerol hyperhydration in trained subjects before exercise in the heat. Int J Sport Nutr Exerc Metab. 2007 Feb;17(1):70-91.
  14. Weiss BA, Powers ME. Creatine supplementation does not impair the thermoregulatory response during a bout of exercise in the heat. J Sports Med Phys Fitness. 2006 Dec;46(4):555-63.
  15. Kilduff LP, Georgiades E, James N, Minnion RH, Mitchell M, Kingsmore D, Hadjicharlambous M, Pitsiladis YP. The effects of creatine supplementation on cardiovascular, metabolic, and thermoregulatory responses during exercise in the heat in endurance-trained humans. Int J Sport Nutr Exerc Metab. 2004 Aug;14(4):443-60.
  16. Rand WM, Pellett PL, Young VR. Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr. 2003 Jan;77(1):109-27.
  17. Trumbo P, Schlicker S, Yates AA, Poos M; Food and Nutrition Board of the Institute of Medicine, The National Academies. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc. 2002 Nov;102(11):1621-30.
  18. Willoughby DS, Rosene JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc. 2003 Jun;35(6):923-9.
  19. Willoughby DS, Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc. 2001 Oct;33(10):1674-81.
  20. Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, Francaux M. Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. J Appl Physiol. 2008 Feb;104(2):371-8.
  21. Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles. Physiol Rev. 2011 Oct;91(4):1447-531.
  22. Harridge SD, Bottinelli R, Canepari M, Pellegrino MA, Reggiani C, Esbjörnsson M, Saltin B. Whole-muscle and single-fibre contractile properties and myosin heavy chain isoforms in humans. Pflugers Arch. 1996 Sep;432(5):913-20.
  23. D’Antona G, Lanfranconi F, Pellegrino MA, Brocca L, Adami R, Rossi R, Moro G, Miotti D, Canepari M, Bottinelli R. Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders. J Physiol. 2006 Feb 1;570(Pt 3):611-27.
  24. Pette D, Peuker H, Staron RS. The impact of biochemical methods for single muscle fibre analysis. Acta Physiol Scand. 1999 Aug;166(4):261-77. Review.
  25. Saremi A, Gharakhanloo R, Sharghi S, Gharaati MR, Larijani B, Omidfar K. Effects of oral creatine and resistance training on serum myostatin and GASP-1. Mol Cell Endocrinol. 2010 Apr 12;317(1-2):25-30.
  26. Tarnopolsky MA. Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem. 2007;46:183-204. Review.
  27. Sakkas GK, Schambelan M, Mulligan K. Can the use of creatine supplementation attenuate muscle loss in cachexia and wasting? Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):623-7. Review.
  28. van Loon LJ, Murphy R, Oosterlaar AM, Cameron-Smith D, Hargreaves M, Wagenmakers AJ, Snow R. Creatine supplementation increases glycogen storage but not GLUT-4 expression in human skeletal muscle. Clin Sci (Lond). 2004 Jan;106(1):99-106.
  29. Derave W, Eijnde BO, Verbessem P, Ramaekers M, Van Leemputte M, Richter EA, Hespel P. Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans. J Appl Physiol. 2003 May;94(5):1910-6.
  30. Op ‘t Eijnde B, Ursø B, Richter EA, Greenhaff PL, Hespel P. Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes. 2001 Jan;50(1):18-23.
  31. Steenge GR, Simpson EJ, Greenhaff PL. Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol. 2000 Sep;89(3):1165-71.
  32. Green AL, Simpson EJ, Littlewood JJ, Macdonald IA, Greenhaff PL. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand. 1996 Oct;158(2):195-202.
  33. Pittas G, Hazell MD, Simpson EJ, Greenhaff PL. Optimization of insulin-mediated creatine retention during creatine feeding in humans. J Sports Sci. 2010 Jan;28(1):67-74.
  34. Sappey-Marinier D, Calabrese G, Fein G, Hugg JW, Biggins C, Weiner MW. Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy. J Cereb Blood Flow Metab. 1992 Jul;12(4):584-92.
  35. Rango M, Castelli A, Scarlato G. Energetics of 3.5 s neural activation in humans: a 31P MR spectroscopy study. Magn Reson Med. 1997 Dec;38(6):878-83.
  36. Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003 Oct 22;270(1529):2147-50.
  37. Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011 Apr;105(7):1100-5.
  38. Delanghe J, De Slypere JP, De Buyzere M, Robbrecht J, Wieme R, Vermeulen A. Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clin Chem. 1989 Aug;35(8):1802-3.
  39. McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007 Sep;14(5):517-28.
  40. Klopstock T, Elstner M, Bender A. Creatine in mouse models of neurodegeneration and aging. Amino Acids. 2011 May;40(5):1297-303. Review.
  41. Bender A, Beckers J, Schneider I, Hölter SM, Haack T, Ruthsatz T, Vogt-Weisenhorn DM, Becker L, Genius J, Rujescu D, Irmler M, Mijalski T, Mader M, Quintanilla-Martinez L, Fuchs H, Gailus-Durner V, de Angelis MH, Wurst W, Schmidt J, Klopstock T. Creatine improves health and survival of mice. Neurobiol Aging. 2008 Sep;29(9):1404-11.
  42. Halestrap AP, Griffiths EJ, Connern CP. Mitochondrial calcium handling and oxidative stress. Biochem Soc Trans. 1993 May;21(2):353-8. Review.
  43. Bangsbo J, Juel C, Hellsten Y, Saltin B. Dissociation between lactate and proton exchange in muscle during intense exercise in man. J Physiol. 1997 Oct 15;504 ( Pt 2):489-99.
  44. McKenna MJ, Heigenhauser GJ, McKelvie RS, MacDougall JD, Jones NL. Sprint training enhances ionic regulation during intense exercise in men. J Physiol. 1997 Jun 15;501 ( Pt 3):687-702.
  45. Huso ME, Hampl JS, Johnston CS, Swan PD. Creatine supplementation influences substrate utilization at rest. J Appl Physiol. 2002 Dec;93(6):2018-22.


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