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Everything you need to know about Creatine

by Tiago Vasconcelos | Sep 18, 2018

What is creatine?

Creatine is an amino acid derivative constructed from arginine, glycine, and methionine. It gained widespread popularity in the early 1990's among athletes and gym-goers, and remains one of the most popular supplements. Among strength and power athletes, its use can get as high as 80%.1

It is produced endogenously by the body in the kidneys, liver, and pancreas at a rate of about 1 gram per day. Creatine can also be obtained from food (particularly red meat), although this is rather small, usually amounting to 1g total in an average omnivorous diet, making the total amount of natural creatine of around 2g per day, with 95% of it being stored in skeletal muscle, and roughly two thirds of that being stored as phosphocreatine (PCr), while the remaining amount of creatine is stored as free creatine.2 Creatine supplementation increases creatine content of muscles by around 20%, reaching a limited saturation of 150-160 mmol/kg.3

Creatine is one of the most extensively studied and scientifically validated supplements for athletes – amounting to hundreds of studies – with 70% of them reporting a significant improvement, and the rest generally reporting non-significant gains.4 It has been regularly shown to increase strength and fat-free mass, with a typical benefit of around 5% to 15%.5 Usually, there is a greater benefit in maximum reps when compared to 1RM. One meta-analysis showed that individuals ingesting creatine combined with resistance training, obtained on average an 8% increase in 1RM strength and a 14% increased performance in maximum reps.6

How does it work?

Creatine has a crucial role in energy metabolism as phosphocreatine (PCr). It's the base to create adenosine triphosphate (ATP) by rephosphorylating adenosine diphosphate (ADP). This is essential in short-duration, high-intensity exercise. The ability of rephosphorylatin ADP depends on an enzyme called creatine kinase, plus the already stored PCr. When the latter gets depleted, high-intensity performance suffers. PCr levels decrease anywhere from 30% to 80% of resting levels, depending on the duration.7 During repeated bouts, it gets almost completely depleted.8

The effect is more pronounced in anaerobic, high-intensity activities (under 30 seconds). It can still have positive effects for up to 150 seconds, but the evidence isn’t as strong the more it shifts to endurance.9

Besides ATP renewal, there are other potential mechanisms involved, ranging from satellite cell proliferation, myogenic transcription factors, and insulin-like growth factor-1 signalling10. There is also speculation that it may change gene expression.11

Growth factor (IGF-1) concentration has shown to be increased, and in at least in one study, changes in lean mass were positively correlated with modified levels of intramuscular IGF-1.12

Pathway of creatine metabolism

Pathway of creatine metabolism - Persky & Brazeau, 2001

Dosing

The most common dosing protocol is a loading period of 3-5 days with 20 to 25 g/d followed by a 3-5 g maintenance dose. When dosing for bodyweight, around 0.3 g/d/kg for loading and 0.03 g/kg/d for maintenance has been used. When using a loading protocol, it’s recommended to split the dose into 3 or 4 smaller doses, otherwise, it can cause diarrhoea and nausea.

When it comes to loading, there are two somewhat competing ideas – some think that loading is necessary, and some think that loading is useless. Neither is quite correct. If you don’t use a loading protocol, you will still reap all the benefits – the only disadvantage being that it takes a longer time to have saturated levels. It will only start being effective in a few weeks, compared to a few days if you front-load. So, if you want to use loading to get the effects faster, that’s fine. And if you don’t want to load and don’t mind taking longer to reap the benefits, that’s fine as well. I personally recommend loading, because I don’t see the point of waiting. It’s also not more expensive, as I’ve seen argued, since the increased dosage is compensated by receiving the benefit earlier, and that’s what you actually care about. 

Some people wonder if creatine needs to be cycled. This is a common protocol with performance-enhancing drugs, however, there is no reason to cycle creatine as there are no accumulative negative side effects of supplementation. It also doesn't decrease in effectiveness over time. While creatine intake appears to downregulate the creatine transporter in animals, this doesn't seem to be the case in humans.13 Some advocate taking a week off or more per year of all supplements, and if you want to do that, that’s fine, but I personally don’t think it’s necessary.

ENHANCING CREATINE 

There may be some advantage to consuming simple carbohydrates along with creatine, at least during the period of saturation. One study found that accumulation was increased by 60% when 5g of creatine was ingested with 93g of simple carbohydrates, compared with taking creatine by itself.14

Another study found that body creatine retention of 5 g CM was increased by 25% with the addition of 50 g of protein and 47 g of carbohydrate, or 96 g carbohydrate when compared to a placebo treatment of 5 g carbohydrate.15

However, this doesn’t automatically mean it will translate to performance. In one study with 10 international caliber swimmers, it made no difference.16

Nevertheless, it might still be worth a try, especially given that it likely just requires athletes to take it with their pre or post workout meals.

WATER RETENTION

Creatine supplementation increases body mass by about 1 to 2 kg in the first week of loading.17 This initial weight gain is simply water, from the enhanced intracellular osmotic gradient, causing water to fill the cell.18

However, long-term studies have shown increases in fat-free mass and/or muscle contractile protein synthesis with no disproportionate increase in total body water19. So, the extra mass beyond the initial gain is in fact muscle mass, not added water retention.

For those worried about making weight, the wash-out period is around 4 weeks20. There is an argument to be made to not discontinue supplementation, as you may lose the performance benefit. However, given that creatine’s ergogenic effect is more long-term, as it actually causes extra muscle mass, I believe cessation of creatine supplementation likely doesn’t cause a performance drop. One study seems to support this, as withdrawal from creatine had no effect on the rate of strength, endurance, and loss of lean tissue mass with 12 weeks of reduced-volume training21. Although the sample was small, and it’s the only study to my awareness. If you don’t want to risk it, then continue with supplementation throughout your competition preparation.  

NON-RESPONDERS

Creatine doesn't seem to work for some people, the so called "non-responders", which account for 20-30% of individuals22. This is hypothesized to be caused by the creatine pool already being saturated, although genetic variations in creatine transport capacity seem to play a role as well23.

Those who have lower muscle creatine stores are more likely to experience muscle storage increases of 20-40%, while those with relatively high muscle stores may only increase half that amount. Creatine content increase is correlated to performance increase.24-6

This is likely because of their diet, which may contain sources that already provide a high amount of creatine. One study shows that 225g (8oz) of beef contains around 2g of creatine, which is quite significant27. These were values for raw meat, but it seems cooking only degrades creatine up to 30%28.

In one study, out of 11 subjects, 3 didn't respond to supplementation. Muscle biopsies were made, and the non-responders had a higher initial level of total muscle creatine content and less percentage of type II fibers.29

Cognitive benefits

Creatine also has a vast number of cognitive benefits. Higher brain creatine is associated with improved neuropsychological performance, and there are deficiency symptoms that result in mental retardation (although it’s very rare).30

Studies have demonstrated that impaired cognitive processing can be improved with creatine supplementation. For this, the dose is usually higher, ranging from 20 to 40 g/d, for younger and older adults respectively. It has also shown some potential for neurodegenerative diseases in animal models, and work is being done on Parkinson’s disease in humans.31-4

There is also evidence of it being beneficial for healthy older adults – improving forward number and spatial recall, long-term memory, and being potentially useful for traumatic brain injuries, reducing headaches, dizziness, and fatigue.35-6

Creatine for vegetarians

Since the main source of creatine is from animal products, it’s a reasonable assumption that creatine supplementation would have a greater benefit, and it seems that’s the case. In one study, vegetarians gained 2.4 kg of lean mass, compared to 1.9 kg of the non-vegetarian group.37

The cognitive benefits that we covered previously also seem to be boosted in vegetarians. This is somewhat odd, considering that while it’s known that vegetarians have lower tissue amounts of creatine (measured directly via muscle biopsy) than omnivores38, brain creatine content doesn’t seem to be affected by creatine intake, suggesting it’s supplied by its endogenous production.39

Nevertheless, in one study, 128 adult females were separated into those who were and were not vegetarian, and vegetarians showed improved memory with supplementation.40 In another study, vegetarians showed improvement in tasks that required speed of processing, like working memory and fluid intelligence (abstract reasoning).41

Forms of creatine

There are countless creatine forms on the market. The most popular being creatine monohydrate, creatine phosphate, creatine citrate, creatine pyruvate, creatine ethyl ester, or creatine nitrate.

Creatine monohydrate is by far the most studied and proven to be both safe and effective. Most forms don’t offer any advantage and are often significantly more expensive42-43. Ironically, despite being advertised as better, some are actually worse.44

The only advantage of some alternative creatine forms is increased solubility and bioavailability, which may alleviate gastrointestinal discomfort.45

Safety

Creatine is an incredibly safe supplement, in so far as any supplement can be safe.

The most common concern is renal function. While creatine does slightly raise creatinine levels, this isn’t accompanied by any negative side effects.46 In healthy individuals, creatine is safe to consume with an appropriate dosage.47-51 In people with a history of renal disease or those taking nephrotoxic medications, there is an increased risk of renal dysfunction, and supplementation is likely not recommended.

Most studies are done short-term, which have caused some people to wonder about long-term effects, but even with supplementation up to 4 and 5 years, it seems to have no adverse health effects.52-3

Beyond the basic safety concerns, there is the worry of creatine causing baldness. Creatine may increase the rate of balding in men with Male Pattern Baldness, since creatine increases DHT, which is implicated in the pathology and a receding hairline.54 One study found an increase of DHT of almost 50% after 3 weeks of supplementation.55

However, it’s worth remembering that young male baldness is heavily genetic.56 If you aren’t prone to baldness, it’s unlikely to affect you. And even if you are, there is no direct evidence of it actually making baldness worse, although there is at the very minimum a mechanism for it. In the end, I wouldn’t worry too much about it unless you’re very concerned about your hair, or you’re genetically prone to it. But at the end of the day, it’s up to you to consider if it’s worth the risk.

Timing

When should you take creatine? The simplest answer is that it doesn’t matter too much, because creatine’s effects aren’t acute. No matter when you take it, you will saturate your skeletal muscle with creatine and reap the benefits.

Nevertheless, it doesn’t mean that there aren’t benefits of a specific timing. It has been hypothesized and recommended for a long time that you should take creatine either before or after your workout.

In one study, 19 healthy recreational male bodybuilders were separated into two groups: 5g of creatine pre-workout or 5g of creatine post-workout.57 It concluded: “The results from this study suggest that consuming creatine monohydrate post exercise may be superior to consuming it pre exercise with regards to improving body composition” Although it did not reach statistical significance.

Image credit: http://suppversity.blogspot.pt

In another study, subjects were split into 3 groups: creatine pre-workout, post-workout, and placebo. The post-workout group saw significantly greater muscle gains than the placebo group, while the pre-workout didn’t.58 However, the difference between before and after supplementation didn't reach statistical significance.


Change (post-training mean – pre-training mean) in lean tissue mass for creatine before (CR-B), creatine after (CR-A), and placebo (PLA) groups.

The evidence for the benefit of taking creatine post-workout isn’t strong, but it’s at least indicative. Given that taking your creatine post-workout compared to any other time of the day is unlikely to add any extra effort, it might be wise to do so, and I recommend it to my clients.

Creatine brands

Generally, the supplement brands don’t matter too much. What matters is the main ingredient, and the benefits will be the same regardless of what brand.

The only concern over supplement brands is impurities and inaccurate dosing. For this reason, many recommend buying Creapure. It’s made in Germany by AlzChem, and undergoes a rigorous testing process to make sure it’s free of impurities and by-products like CRN (creatinine), DCD (dicyandiamide), and thiourea. It’s a bit more expensive, but at least you have some guarantee of quality. Otherwise, they may be made in third world countries, with likely little concern about quality. Although this is a concern even in modern countries.

Alternatively, you can check individual products. Labdoor is an independent company that tests supplements. They send a sample of each product to an FDA-registered laboratory for a detailed chemical analysis, which includes measurements of active ingredients and potential contaminants.  Here are the top 5 products out of the 25 they analyzed:



You can check the full list here: https://labdoor.com/rankings/creatine


Caffeine interaction

Some have claimed that caffeine counteracts creatine. For example, in one study, the addition of caffeine to creatine blunted intermittent force production, despite not altering muscular creatine content.59 Although its negative effects don’t seem to be consistent.60-1

A recent study last year with mice concluded that "caffeine administration does not impair skeletal muscle load-induced mTOR signalling, protein synthesis, or muscle hypertrophy”.62 and in another study, comparing creatine and caffeine with the combination of both, found that caffeine potentiates the effects of creatine during a physical exercise.63


In a 2015 review, the authors recommended avoiding chronic, high-dose caffeine intake to maximize the ergogenic effect of creatine supplementation.64 If you want to play it safe until the evidence solidifies, that may be the best option.

Conclusion

Creatine is close to the best supplement you can possibly take. It’s very well understood, cheap, safe, and effective. A very rare combination in almost all sports supplements available. Since the article is a bit long, here at some take-home points:

  • Creatine works by enhancing the ATP-PCr energy system by better maintaining muscle ATP levels
  • Creatine has been shown repeatedly to be both safe and effective
  • Not everyone responds to supplementation
  • Beyond helping strength and body compositions, there also seems to be cognitive benefits
  • Creatine monohydrate is the best and cheapest form
  • Dosage should be around 20g for 5 days when loading, and 5g afterwards
  • There is no inherent need to cycle it
  • Might be best to avoid taking with high doses of caffeine
  • Taking creatine post-workout and/or with carbohydrates may have an advantage


References

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