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Creatine 101: What It Is and What It Does

Creatine is the undisputed king of sports nutrition supplements, but how does it work and what are the benefits of this best-selling pre-workout ingredient?

Over the past 20 years, sports nutrition has escalated by leaps and bounds, and in that time, athletes, bodybuilders, and casual gym rats have been inundated by all sorts of shiny new herbal extracts, synthetic ergogenics, and isolated amino acids that promise to deliver life-changing results. Yet, few of these compounds have ever delivered on the hype.

There has been a compound, however, that’s been a staple of lifters and athletes for decades prior to the explosion in popularity of sports nutrition supplements. That ingredient is none other than creatine monohydrate.

Most of you reading this have heard of creatine, and you’ve probably even experienced some of the benefits of creatine supplementation for yourself, such as enhances lean mass gains or better athletic performance.

But, how does creatine work? Is creatine safe for women? And, how much creatine should I take?

We’ve got all these questions answered and a whole lot more in store as we take an in-depth look at creatine — the king of sports supplements.

What is Creatine?

Creatine is a substance naturally produced in the body from the amino acids glycine, arginine, and methionine. [1,2] Chemically, creatine is known by the name α-methyl guanidine-acetic acid, but seeing as this isn’t a biochemistry course, we’ll leave it at just plain old creatine.

Creatine is primarily stored (~95%) in your skeletal muscles in the form of phosphocreatine, and the remaining 5% is stored in the kidneys, liver, and brain. [1] It’s also found in a number of other foods in our diet, especially red meat.

Now, the amount of creatine each of us stores in our body is going to depend on a few factors, including:

  • Exercise
  • Amount of Lean Muscle Mass
  • Levels of Anabolic Hormones such as IGF-1 (insulin-like growth factor-1) and Testosterone
  • Meat Consumption

What Does Creatine Do?

Following ingestion, creatine binds to a molecule of phosphate to form phosphocreatine or creatine phosphate.

Why is this important?

Whenever you ingest nutrients (whole foods, protein powder, BCAAs, etc.), your digestive system breaks down these nutrients to get energy so that it can power all of the other chemical and physiological processes that go on in the body.

These processes require energy in the form of ATP (adenosine triphosphate). ATP also serves as the primary fuel for your muscles during high-intensity exercise like resistance training or sprinting.

The way ATP provides energy is by donating one of its three phosphate groups (remember ATP stands for adenosine TRI-phosphate, meaning it has three phosphates attached to one molecule of adenosine).

After donating its phosphate group, ATP now becomes ADP (adenosine DI-phosphate), meaning it has two phosphates instead of three.[1] Now, the body can readily use ATP for energy production, but it’s not so fond of ADP for generating energy. So, your body reserves this ADP molecule and saves it until another phosphate is freed up and it can be recycled into ATP.

Now, here’s where creatine enters the picture.

As we mentioned above, creatine is stored in the body as phospho-creatine, meaning it has an extra phosphate molecule to donate. Creatine, being the noble fellow that it is, sacrifices its phosphate group for the good of your body, donating it to ADP and transforming the seemingly useless ADP into the energy-producing powerhouse that is ATP.

Therefore, the primary benefit of creatine resides in its ability to rapidly regenerate ATP, which translates to a number of performance and physique benefits that we’ll discuss in more detail now!

Benefits of Creatine

Improves ATP Production

As we just mentioned, the primary benefit of ATP comes from its ability to rapidly replenish ATP stores in the body.

ATP serves as the “cellular currency” of energy production in the body, meaning that once your ATP stores are empty, your body has to start breaking down glycogen or pulling in glucose and fats from the bloodstream to power your muscles during training. So, the more ATP you have, the longer you can train before succumbing to fatigue, which leads to greater gains in size, strength, and performance. [1,2] 

Muscle Builder

Creatine has been extensive studies and shown time after time to improve lean body mass (a.k.a. Muscle mass) as well as performance during intense training. [4,5] Studies note that supplementing with creatine monohydrate while performance resistance training increase muscle cell nuclei concentration, which promotes the greater growth of lean muscle. [6]

Other research notes that when creatine and weight lifting are combined, it increases fat-free mass (i.e. muscle), muscle morphology, and physical performance. [7]

Part of this is due to creatine’s ability to help you grind out more reps (due to better energy production), but creatine also helps stunt myostatin production. [8] In case you weren’t aware, myostatin is a devious little protein that puts the brakes on muscle growth in the body. By inhibiting it, creatine helps promote greater muscle cell growth and differentiation.

Strength Booster

One of the truly exceptional things about creatine is that not only does it help muscles to grow bigger, it also helps them become stronger, too. Research has shown that weightlifters using creatine increased their one-rep max on bench press of 43%, compared to those who did not use creatine while training. [9,10]

Hydration Support

We’ve spent the majority of this article discussing the primary function of creatine, in regards to its ability to enhance ATP regeneration in the body, but it also serves another very important role in regards to health and performance.

Creatine monohydrate also functions as a natural osmolyte, that helps increase the water content within muscle cells. [15] Because of this cell-hydrating effect, creatine increases cell volume, which has a multitude of benefits including better stamina, bigger “water” pumps, and muscle growth.

Brain Booster

Up top, we mentioned that the majority of creatine is stored in the brain, but a small percentage is also stored in your brain. As it turns out, creatine supplementation also imparts some brain gains as well, especially for vegans and vegetarians.

Research notes that when adult vegetarians supplemented with creatine, they experienced better working memory and intelligence. The reason vegetarians were used for the study was that they tend to have low levels of endogenous creatine due to their low meat intake. [12,13]

But that’s not all…

Creatine has also been shown to improve mental performance following 36 hours of sleep deprivation [14], making this a great supplement to use if you’re one who doesn’t get adequate amounts of sleep each night.

Neuroprotector

Creatine not only helps our brains to function at a higher level, but it may also protect us from certain neurological diseases as well. Supplemental creatine can act as a substrate for creatine kinase, which may increase phosphocreatine and protect against ATP depletion, which has been documented to exert neuroprotective benefits. [17]

Other studies note that supplementing with creatine can improve quality of life and reduce symptoms in individuals with cognitive dysfunction. [16] Furthermore, creatine supplementation has been documented to prevent up to 90% of the decline in dopamine levels in animals. [17]

You may be asking, “why is that important?”

Well, chronically falling levels of dopamine production are a tell-tale sign of Parkinson’s disease.

Additional research has noted that when patients with Parkinson’s were given creatine it reduced their decline in cognitive function and increased their strength. [18,19]

Improves Symptoms of Depression

Consuming creatine daily has been noted to lessen symptoms of depression in women, including ones who didn’t respond to SSRI prescriptions (the “standard” treatment for depression). [20]

Additional studies have documented that creatine supplementation is beneficial for the treatment of a number of other diseases including [21,22,23]: 

  • Alzheimer’s
  • Ischemic Stroke
  • Huntington’s Disease
  • Amyotrophic Lateral Sclerosis
  • Epilepsy
  • Brain or Spinal Cord Injuries

Combats Fatigue

We’ve mentioned previously that creatine improves stamina and endurance via improve ATP production, but it also helps you last longer during your workouts due to its unique ability to reduce neuromuscular fatigue and perceived fatigue when training.[24,25]

Creatine also has been shown to boost mood following sleep deprivation or psychologically-intensive tasks. [26]

Improves Injury Recovery Rate

Not only does creatine improve your performance on the field, it also helps you get back there following an injury. Research conducted in healthy subjects has shown that creatine supplementation significantly improves recovery of knee extensor muscle function after injury. [33]

Heart Helper

In addition to its role in muscle building, creatine also helps fortify your cardiovascular system as well, protecting the heart against stress and improving its ability to repair. [29]

Creatine production also helps reduce homocysteine levels, which if you weren’t aware, elevated levels of homocysteine are associated with an increased risk of cardiovascular disease.

Further research has shown that when creatine is supplemented at a dose of 20 grams per day, it lowers cholesterol. [30]

Supports Skeletal System

Creatine enhances osteoblast formation, which increases bone formation and bone repair. [31] Additional research in older women with osteoarthritis has noted that creatine supplementation helps reduce pain associated with the disorder. [32]

Steadies Blood Sugar

We’re still not done with the benefits of creatine yet!

As you well know, type 2 diabetes and metabolic syndrome are two of the most common chronic diseases affecting our population these days. At the core of these two diseases is a combination of chronically elevated blood sugar levels and insulin resistance.

As it turns out, creatine might be an unsung hero of sorts for diabetics. Research notes that supplementing with creatine can significantly reduce blood sugar measurements during a glucose tolerance test in healthy men performing aerobic exercise. [27]

A 2016 systematic review also confirmed these findings when it concluded that creatine is useful for controlling blood glucose when combined with exercise. [28]

Beneficial for Expectant Mothers

Studies involving pregnant women have noted that supplementing with creatine can benefit baby development in the instances of oxygen deprivation or premature birth. [34]

Potential Testosterone Booster

The final benefit of creatine is more of an “outlier” of sorts, as it’s never really been thoroughly investigated, but still, warrant mentioning.

In addition to all of the muscle and performance benefits mentioned prior, creatine may also boost the most anabolic hormone of all — testosterone.

Research using very high doses of creatine (100mg/kg) noted that it successfully increased testosterone levels. [11]

How much is that for the average man?

For the average 175lb male, you’d need around 8 grams of creatine to get the potential testosterone boosting benefits of this all-time muscle builder.

Speaking of dosing…

How Much Creatine Should I Take?

All sorts of dosing and loading protocols have been used with creatine studies over the years.

Some protocols call for loading up to 20 grams per day (divided into 4-5 doses) for 3-4 days to accelerate the rate of saturation, but for the average lifter looking to experience all that creatine has to offer, a standard dose of 5 grams per day every day of creatine monohydrate is recommended.

When to Take Creatine

The great thing about creatine, unlike other supplements, is that you really can take it any time of day. You see, you start to experience the benefits of creatine once your muscles are saturated with it. It doesn’t offer an acute benefit, like what caffeine or citrulline malate does.

Therefore, you can take your creatine pre-workout, post workout, intra-workout, or any other time of day. It doesn’t really matter so long as you get your 5 grams in every day.

However, there can be an argument made for an “optimal” time to take creatine is the post-workout period, when insulin sensitivity is highest, meaning it will be rapidly taken up and stored in your muscles. But again, so long as you’re taking in your 5 grams of creatine monohydrate every day, you will be fine.

Takeaway

Creatine monohydrate has stood the test of time as the de facto king of the supplement world. It’s proven time and time again to enhance lean mass, strength, power, and performance. Creatine also comes with a drove of other benefits for your brain and heart, too.

When you add it all together, creatine supplementation is really a no-brainer and should be a part of every fitness enthusiasts stack, young or old, male or female.

References

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  17. Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157(1):142-149. doi:10.1006/exnr.1999.7049.
  18. Li Z, Wang P, Yu Z, et al. The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson’s disease. Eur Neurol. 2015;73(3-4):205-211. doi:10.1159/000377676.
  19. Hass CJ, Collins MA, Juncos JL. Resistance training with creatine monohydrate improves upper-body strength in patients with Parkinson disease: a randomized trial. Neurorehabil Neural Repair. 2007;21(2):107-115. doi:10.1177/1545968306293449.
  20. Kondo DG, Sung Y-H, Hellem TL, et al. Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: A 31-phosphorus magnetic resonance spectroscopy study. Journal of affective disorders. 2011;135(0):354-361. doi:10.1016/j.jad.2011.07.010.
  21. Bürklen TS, Schlattner U, Homayouni R, et al. The Creatine Kinase/Creatine Connection to Alzheimer’s Disease: CK Inactivation, APP-CK Complexes, and Focal Creatine Deposits. Journal of Biomedicine and Biotechnology. 2006;2006:35936. doi:10.1155/JBB/2006/35936.
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  24. Smith AE, Walter AA, Herda TJ, et al. Effects of creatine loading on electromyographic fatigue threshold during cycle ergometry in college-aged women. Journal of the International Society of Sports Nutrition. 2007;4:20. doi:10.1186/1550-2783-4-20.
  25. Hadjicharalambous M, Kilduff LP, Pitsiladis YP. Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation. Journal of the International Society of Sports Nutrition. 2008;5:14. doi:10.1186/1550-2783-5-14.
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  27. Gualano B, Novaes RB, Artioli GG, et al. Effects of creatine supplementation on glucose tolerance and insulin sensitivity  in sedentary healthy males undergoing aerobic training. Amino Acids. 2008;34(2):245-250. doi:10.1007/s00726-007-0508-1.
  28. Pinto CL, Botelho PB, Pimentel GD, Campos-Ferraz PL, Mota JF. Creatine supplementation and glycemic control: a systematic review. Amino Acids. 2016;48(9):2103-2129. doi:10.1007/s00726-016-2277-1.
  29. Spindler M, Meyer K, Stromer H, et al. Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. Am J Physiol Heart Circ Physiol. 2004;287(3):H1039-45. doi:10.1152/ajpheart.01016.2003.
  30. Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci (Lond). 1996;91(1):113-118.
  31. Gerber I, ap Gwynn I, Alini M, Wallimann T. Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures. Eur Cell Mater. 2005;10:8-22.
  32. Neves MJ, Gualano B, Roschel H, et al. Beneficial effect of creatine supplementation in knee osteoarthritis. Med Sci Sports Exerc. 2011;43(8):1538-1543. doi:10.1249/MSS.0b013e3182118592.
  33. Cooke MB, Rybalka E, Williams AD, Cribb PJ, Hayes A. Creatine supplementation enhances muscle force recovery after eccentrically-induced muscle damage in healthy individuals. Journal of the International Society of Sports Nutrition. 2009;6:13. doi:10.1186/1550-2783-6-13.
  34. Dickinson H, Ellery S, Ireland Z, LaRosa D, Snow R, Walker DW. Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy. BMC Pregnancy and Childbirth. 2014;14:150. doi:10.1186/1471-2393-14-150.
  35. Jäger, Ralf; Analysis of the Efficacy, Safety, and Regulatory Status of Novel Forms of Creatine. Amino Acids 40.5 (2011): 1369-383.
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